We have reported that duodenal mucosa rapidly disposes of both acid
and alkali in vitro; neither property being altered by gassing with N2
while iodoacetate was in the perfusing solutions. While acid disposal
progressively decreased with time in complementary experiments with in
vitro gut sacs, with in vivo gut sacs no fatigue was evident raising the
possibility of an active component in the properti...
We have reported that duodenal mucosa rapidly disposes of both acid
and alkali in vitro; neither property being altered by gassing with N2
while iodoacetate was in the perfusing solutions. While acid disposal
progressively decreased with time in complementary experiments with in
vitro gut sacs, with in vivo gut sacs no fatigue was evident raising the
possibility of an active component in the properties [1].
Upon reflection, the most important point to be made from this study
is that in the absence of active transport processes the interstitial pH
of a tissue will tend towards 7.40 provided the extracellular are
maintained by keeping the pCO2 and [HCO3-] at 40mmHg and 25mmol
respectively. Upon death the pCO2 should equilibrate with that in
atmospheric air [0.3 mmHg] but the [HCO3-] should fall in this open
system and the pH remain the same until the body temperatue falls when it
should tend to rise above pH 7.40. In other words the development of an
intramucosal acidosis must be the product of an active transport process
and therefore a potentially beneficial adaptive response to a fall in body
temperature and/or to the development of an energy deficit.
It would seem therefore, that the primary effect of ATP synthase
might be to catalyse the active pumping of protons out of the
mitochondrial matrix to establish and maintain the protonmotive force
needed to drive ATP resynthesis by oxidative phosphorylation. In removing
protons from the cytosol that would have the reverse effect, the two
opposing processes both involving ATP synthase and accounting for the
active component we appear to have identified in our studies of duodenal
mucosa.
It transpires that protons passing through ATP synthase release ATP
from its membrane bound form and that ATP synthesis may still occur when
oxidative phosphorylation is inhibited but remains membrane bound. In
which case the in situ hydrolysis of membrane bound ATP might be
responsible not only for pumping of protons into the cytosol but also for
the generation of heat. Indeed the most striking feature of dying and
death is a fall in body temperature and not necessarily a fall in
intramucosal pH although it is usually present. Thus the fall in
intramucosal pH, and accompanying oxygen supply dependency, might be
adaptive responses to metabolic stresses which fails as death approaches.
Preconditioning might, therefore, be due to priming of the
protonmotive force needed to replenish ATP stores by oxidative
phophorylation in addition to limiting the likelihood of free radical
injury upon reoxygenation/perfusion.
Cardiovascular physiologists have focused their attentions on the
Na+-H+ exchanger and Na+-HCO3- importer in their considerations of
myocytic cytosol acid base balance [3,4]. It may well be that these are
secondary events modulating those hypothetically catalysed by
mitochondrial ATP synthase.
References
(1). Fiddian-Green RG, Silen W. Mechanisms of disposal of acid and
alkali in rabbit duodenum.
Am J Physiol. 1975 Dec;229 [6]:1641-8.
(2). Berg JM, TymoczkoJL, Stryer L. Biochemistry. Fifth editon. WH
Freeman and Company, New York, 2002.
(3). Levick JR. Cardiovascular physiology. Arnold, London, 2004.
(4). Lionel H. Opie. The Heart: Physiology, from cell to circulation.
Philadelphia, Lippincott–Raven, 1998.
I read with great interest the published study by Urhausen
et al. [1] It is known that anabolic steroid use in athletes
has become a major medical issue. Although Urhausen et al.
found that left ventricular wall thickness related to
fat-free body mass did not differ between users and
ex-users, Sachtleben et al. [2] previously reported that the
parameters of left ventricular thickness showed si...
I read with great interest the published study by Urhausen
et al. [1] It is known that anabolic steroid use in athletes
has become a major medical issue. Although Urhausen et al.
found that left ventricular wall thickness related to
fat-free body mass did not differ between users and
ex-users, Sachtleben et al. [2] previously reported that the
parameters of left ventricular thickness showed significant
differences between nonusers and users. Apart from this,
Sachtleben et al. also demonstrated that maximal oxygen
consumption in the anabolic steroid user group was lower
than that of nonuser group. In other words, a decrease in
shortening fraction of left ventricle was also observed
between users off and user on groups. This may indicate
non-adaptive changes within the myocardium, and thus cause
the heart to become a less effective pump. Furthermore,
Pearson et al. [3] found that left ventricular diastolic
functions were reduced in a group of anabolic steroid user.
It strikes me that myocardium is over stimulated to
irregular grow by anabolic steroids, and they may lead to
cell disarray in the myocardium, like as hypertrophic
cardiomyopathy. Completely recovery to pre-training
ventricular morphology is not obtained even though anabolic
steroids are discontinued for a long time period.
References
1. Urhausen A, Albers T, Kindermann W. Are the cardiac
effects of anabolic steroid abuse in strength athletes
reversible? Heart 2004;90:496-501.
2. Sachtleben TR, Berg KE, Elias BA, Cheatham JP, Felix GL,
Hofschire PJ. The effects of anabolic steroids on
myocardialstructure and cardiovascular fitness. Med Sci
Sports Exer 1993;25:1240-1245.
3. Pearson AC, Schiff M, Mrosek D, Labovitz AJ, Williams GA.
Left ventricular diastolic function in weight lifters. Am J
Cardiol 1986;58:1254-1259.
La Vecchia et al. [1] considered increased cardiac troponin on admission to be the strongest independent predictor of mortality in acute pulmonary embolism. They attributed the increased troponin to right ventricular involvement, because they excluded patients with known or prior coronary artery disease in their study. The criteria they used for exclusion were documented angina, previous myocardial...
La Vecchia et al. [1] considered increased cardiac troponin on admission to be the strongest independent predictor of mortality in acute pulmonary embolism. They attributed the increased troponin to right ventricular involvement, because they excluded patients with known or prior coronary artery disease in their study. The criteria they used for exclusion were documented angina, previous myocardial infarction, coronary angioplasty or bypass surgery.
But they have not excluded coronary embolism which can occur in patients without prior, known coronary artery disease. As a matter of fact, paradoxical coronary embolism has been reported in patients with increased pulmonary artery pressure, e.g. pulmonary embolism [2,3] or increased right atrial pressure, e.g. Valsalva maneuver or cough.[2-4] It also accounts for ST segment elevation in right precordial leads on ECG in patients with acute pulmonary embolism.[5,6] Paradoxical coronary embolism may contribute to the increased mortality in patients with acute pulmonary embolism.[7,8] Finally, the diagnosis of paradoxical embolism in acute pulmonary embolism carries an important therapeutic implication, because patent foramen ovale, the commonest cause of paradoxical embolism, can now be closed nonsurgically.[9]
References
1. La Vecchia L, Ottani F, Favero L, Spadaro GL, Rubboli A, Boanno C, Mezzena G, Fontanelli A, Jaffe AS: Increased cardiac troponin I on admission predicts in-hospital mortality in acute pulmonary embolism. Heart 2004;90:633-637.
2. Cheng TO: Paradoxical embolism. A diagnostic challenge and its detection during life. Circulation 1976;53:565-568.
3. Cheng, TO: Paradoxic embolism. Am Heart J 1996;131:1238.
4. Cheng TO: Paradoxical embolism: diagnosis and management. J Emerg Med 2001;20:416-417.
5. Cheng TO: Right-sided chest-lead abnormalities on EKG in acute pulmonary embolism. J Nat Med Assoc 2003;95:862.
6. Cheng TO: Brugada syndrome vs pulmonary embolism vs paradoxical embolism. What are we to believe? Int J Cardiol 2004;94:119.
7. Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD, Rauber K, Iversen S, Redecker M, Kienast J: Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997;30:1165-1171.
8. Konstantinides S, Geibel A, Kasper W, Olschewski M, Blümel L, Just H: Patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism. Circulation 1998;97:1946-1951.
9. Cheng TO: Percutaneous closure of patent foramen ovale is the procedure of choice for paradoxical embolism. Circulation 2003;108:e126.
We read with great interest the article by Jaster et al. [1] dealing
with the failure by aspirin and clopidogrel to inhibit platelet
activation during vascular brachytherapy after percutaneous coronary
intervention, which is responsible for a higher risk of stent thrombosis.
With respect to the above, we would like to inform about some findings
dealing with this issue.
We read with great interest the article by Jaster et al. [1] dealing
with the failure by aspirin and clopidogrel to inhibit platelet
activation during vascular brachytherapy after percutaneous coronary
intervention, which is responsible for a higher risk of stent thrombosis.
With respect to the above, we would like to inform about some findings
dealing with this issue.
Platelet aggregation occurs after platelet activation. Several
mechanisms and factors converge to this end including membrane integrin
glycoprotein IIb/IIIa and the membrane receptors for fibrinogen as well as
the calcium-dependent linkage formation between activated receptors and
bivalent fibrinogen resulting in platelet aggregation. The role played by
the pro-aggregation mediators such as ADP, ATP, platelet factor 4 (PF4),
betathromboglobulin (beta-TG), thromboxane A2 (TXA2), fibrinogen and
thrombospondin, which are followed by the translocation of the alpha
granule membrane protein P-selectin (CD62) should be taken into account.
In addition, the role played by phosphatidylserine, which is the starting
point for the coagulation cascade should be taken into account. Despite
all the above, we think that the most important factor should be referred
to the serotonin content into the platelets (p-5HT). Many research studies
have demonstrated the primary role played by p-5HT in the haemostatic
process.[2-5] We demonstrated that platelet serotonin content rather than
platelet count should be considered as the appropriate index for measuring
thrombostasis, since the former parameter and not the latter correlates
with bleeding stoppage. [2] Similar findings have been reported by other
authors measuring these parameters in an experimental model of ITP in
mice. [6] Serotonin is stored in the delta granules of platelets and its
release increase during activation. [7] Stimulated platelets use serotonin
to enhance their retention of procoagulant proteins on the cells surface.
[8] Furthermore, the presence of serotonin is covalently linked to
fibrinogen bound on the surface of the activated platelet where it
increases the retention of procoagulant factors on the cell surface. [8]
Serotonin, therefore, plays a central role in the haemostatic process and
its release is considered the most reliable assay for platelet activation.
[7]
Considering that aspirin reduces platelet aggregation by means of a
prostaglandins-mediated mechanism that interferes with platelet serotonin
uptake and reduces p-5HT values, [2-5] all factors interfering with
platelet serotonin depletion should enhance platelet aggregability. With
respect to the above, we found that long-time consumers of prostaglandins
inhibitors presented with low levels of p-5HT. [9] This finding is
consistent with the fact that tianeptine, a drug which increase platelet
serotonin content is able to stop bleeding in patients affected by
idiopathic thrombocytopenic purpura, whereas drugs which deplete platelet
serotonin content (serotonin uptake inhibitors) and serotonin releasing
agents were able to trigger bleeding within the first 3-4 weeks of
administration, in ITP patients. [9] These findings fit well with the
report by Gurbel et al. [10] demonstrating the failure of clopidogrel plus
aspirin therapy addressed to reduce platelet reactivity.
Summarizing all the above, we believe that the failure by aspirin and
clopidogrel to inhibit platelet aggregation in long-term treated patients
should be associated to the progressive reduction of p-5HT levels.
References
1.Jaster M, Fuster V, Rosenthal P, Pauschinger M, Tran QV, Janssen
D, Hinkelbein W, Schimmbeck P, Schultheiss HP, Rauch U. Catheter based
intracoronary brachytherapy leads to increased platelet activation. Heart
2004, 90:160-164
2.Lechin F, van der Dijs B, Orozco B, Jahn E, Rodriguez S, Baez S.
Neuropharmacological treatment of refractory idiopathic thrombocytopenic
purpura: roles of circulating catecholamines and serotonin. Thromb Haemost
2004; 911254-1256.
3.Lechin F, van der Dijs B, Orozco B, Rodriguez S, Baez S. Elective
stenting, platelet serotonin and thrombotic events (Letter). Platelets
2004; (In press).
4.Lechin F, van der Dijs B. Platelet serotonin and thrombostasis. J
Clin Invest Online (Letters) April 21, 2004.
5.Lechin F, van der Dijs B. Platelet aggregation, platelet serotonin
and pancreatitis (Letter). J Pancreas (Online) 2004; 5:8001-3.
6.Dominguez V, Govezensky T, Gevorkian G, Larralde C. Low platelet
counts do not cause bleeding in an experimental model of immune
thrombocytopenic purpura in mice. Haematologica 2003; 88:679-87.
7.Gobbi G, Mirandola P, Tazzari P, Ricci F, Caimi L, Cacchioli A, et
al. Flow cytometry detection of serotonin content and release in resting
and activated platelets. Br J Haematol 2003; 121: 892-6.
8.Dale GL, Friese P, Batar P, Hamilton SF, Reed GL, Jackson KW, et
al. Stimulated platelets use serotonin to enhance their retention of
procoagulant proteins on the cell surface. Science 2002; 415:175–9.
9.Lechin F, van der Dijs B, Lechin ME. Neuropharmacological therapy
of diseases associated with uncoping stress profile (Th-2 autoimmune
diseases). In: Lechin F, van der Dijs B, Lechin ME, eds. Neurocircuitry
and Neuroautonomic Disorders. Reviews and Therapeutic Strategies. Basel:
Karger, 2002;75-82.
10.Gurbel PA, Samara WM, Bliden KP. Failure of clopidogrel to reduce
platelet reactivity and activation following standard dosing in elective
stenting: implications for thrombotic events and restenosis. Platelets
2004; 15:95-9.
The induction of ischaemia is accompanied by a fall in tissue pH. The
fall is probably due to unreversed ATP hydrolysis rather than the
accumulation of lactate. Stochiometric examination reveals that there is
no net gain of protons during anaerobic glycolysis. Furthermore the degree
of acidosis induced is not reduced by inhibiting glycolysis with
iodoacetate and oxidative phosphorylation with KCN and ca...
The induction of ischaemia is accompanied by a fall in tissue pH. The
fall is probably due to unreversed ATP hydrolysis rather than the
accumulation of lactate. Stochiometric examination reveals that there is
no net gain of protons during anaerobic glycolysis. Furthermore the degree
of acidosis induced is not reduced by inhibiting glycolysis with
iodoacetate and oxidative phosphorylation with KCN and can be fully
accounted for by unreversed ATP hydrolysis.[1,2]
The resyntheis of ATP is directly related to the degree of acidosis
induced for it is a measure of the magnitude of the protonmotive force
driving ATP resynthesis by oxidative phosphorylation (3). Although the
protonmotive force is the pH gradient between the cytosol and
mitochondrial matrix, and the interstitial pH falls between the two, the
three pHs changingin parallel with changes in temperature so that the
magnitude of the gradient is maintained. This is important for the energy
is a linear function of the pH and an exponential function of [H+]. The
beneficial effect of the pH-stat protocol relative to the alpha-stat
protocol during cardiopulmponary bypass reflects the magnitude of the
protonmotive force which falls as the temperature falls but is maintained
by fixing the pH at 7.40 by increasing paO2 in the pH-stat protocol.
Allowing the pH to rise or making it rise artificially generates
lactate [4] and is, therefore, a stimulus for anaerobic glycolysis and an
inhibitor or oxidative phosphorylation. Anaerobic glycolysis is the
preferred and exclusive means of generating ATP in many perfused tissues
including healing wounds [5] and does so without causing a fall in tissue
pH unless there is a pathologic reason for it, such as hypovolaemia. The
implication is that oxidative phosphorylation stops completely for
unreversed ATP hydrolysis caused by impaired oxidative phosphorylation
should be accompanied by a fall in tissue pH. [It appears to be the fall
in pH that opens the K+(atp) channel in a dose related manner].
If so what stops oxidative phosphorylation? A reversal of ATP
synthase, an action designed to use the established ATP pool to pump
protons out of the mitochondria and maintain the protonmotive force so
that ATP resynthesis can resume at an accelerated rate as soon as
metabolic circumstances are reversed? In which case preconditioning might
be due to the upregulation of those enzymes, possibly the nuclear enzyme
poly(ADP-ribose) polymerase, responsible for reversing ATP synthase. The
action might even be an all or nouthing one in each cell for partial
inhibition might allow unwanted protons to accumulate and the pH to fall.
One advantage of inhibiting oxidative phosphorylation is that it should
prevent the generation of free radicals. A better cliniocal understanding
of these issues requires more effective metabolic monitoring.[6]
2. Fiddian-Green RG. Monitoring of tissue pH: the critical
measurement.
Chest. 1999 Dec;116(6):1839-41.
3. Cain, SM: pH effects on lactate and excess lactate in relation to
O2 deficit in hypoxic dogs. J Appl Physiol 1977, 42:44
3. Fiddian-Green RG. Rapid responses to: Vipin Zamvar, David
Williams, Judith Hall, Nicola Payne, Clare Cann, Karen Young, S
Karthikeyan, and John Dunne
Assessment of neurocognitive impairment after off-pump and on-pump
techniques for coronary artery bypass graft surgery: prospective
randomised controlled trial
BMJ 2002; 325: 1268
4. Cain, SM: pH effects on lactate and excess lactate in relation to
O2 deficit in hypoxic dogs. J Appl Physiol 1977, 42:44
5. Wilmore DW, Stoner HB. The wound-organ. in Scientific Foundations
of Trauma. Cooper GJ, Dudley HAF, Gann DS, Little RA, Maymnard RL, Eds.
Butterworth/Heinemann, Oxford. 1997, Chapter 38, pp524-529.
6. Khan AU, Delude RL, Han YY, Sappington PL, Han X, Carcillo JA,
Fink MP. Liposomal NAD(+) prevents diminished O(2) consumption by
immunostimulated Caco-2 cells.
Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L1082-91.
6. Worshipping false gods
Richard G Fiddian-Green (24 September 2003) Electronic letter re: David
Roy Dantzker
Monitoring Tissue Oxygenation : The Quest Continues
Chest 2001; 120: 701-702
We were interested to read Dr Thorne’s article on pregnancy in heart
disease and have been developing our service locally for pregnancy in
congenital heart disease.[1] We have been particularly concerned with the
counselling and management of women following Mustard procedure as many of
this unique group are now of child bearing age and there is little data as
to their pregnancy outcome.[2]
We were interested to read Dr Thorne’s article on pregnancy in heart
disease and have been developing our service locally for pregnancy in
congenital heart disease.[1] We have been particularly concerned with the
counselling and management of women following Mustard procedure as many of
this unique group are now of child bearing age and there is little data as
to their pregnancy outcome.[2]
We carried out a case note review of the 18 women followed up at our
institution after Mustard procedure for simple transposition of the great
arteries. Seven women had a total of eight pregnancies that they intended
to carry to term. The mean age at conception was 24.5 years (range 19-31
years). Five women (six pregnancies) were in NYHA class 1 and had good
ventricular function before conception. All six babies were born without
neonatal complication. No change in patient's exercise tolerance was
reported in the year following each delivery, however two had
deterioration in cardiac function on echo. Subsequently one went on to
require cardiac transplant 11 years following delivery (31 years following
the Mustard procedure). Two women were in NYHA 2 at conception. One was 31
years of age and had poor systemic ventricular function. She was admitted
18 weeks pregnant requiring intra-venous inotropes. She was counselled as
to the risks of continuing her pregnancy and decided against termination.
She died 25 weeks pregnant following a VF arrest. The second patient (28
years old) presented 38 weeks pregnant with poor cardiac function. In view
of deteriorating maternal condition caesarean section was performed.
Following delivery she remains in heart failure despite maximal therapy
and is currently on the active cardiac transplant list.
In our series, as others have described, asymptomatic women with good
echocardiographic function tolerate pregnancy well. [3] At the moment our
limited data suggests that outcome of pregnancy in symptomatic patients
with atrial switch procedure can be disastrous with life threatening
deterioration of their ventricular function. The role of exercise testing
and assessment of systemic ventricular performance under loading
conditions mimicking pregnancy may have a place in this group of patients
prior to preconception counselling. Given the potential for development of
impaired systemic ventricular function in all patients following Mustard
procedure we agree with Dr. Thorne’s suggestion that earlier pregnancy
should perhaps be advised.
References
1) Thorne SA. Pregnancy in heart disease. Heart 2004;90:450-456
2) Moons P, Gewillig M, Sluysmans T, et al. Long term outcome up to
30 years after the Mustard or Senning operation: a nationwide multicentre
study in Belgium. Heart 2004;90:307-313
3) Clarkson PM, Wilson NJ, Neutze JM, et al. Outcome of pregnancy
after the Mustard operation for transposition of the great arteries with
intact ventricular septum. J Am Coll Cardiol 1994;24:190-193
I read the article by Urhausen et al. “Are the cardiac effects of
anabolic steroid abuse in strength athletes reversible?” with great
interest, however there are several factors that should be discussed.[1]
First, the only subjects with left ventricular posterior wall measurements
beyond normal limits were the users, which were only slightly enlarged
>11.4 mm. We previously reported on...
I read the article by Urhausen et al. “Are the cardiac effects of
anabolic steroid abuse in strength athletes reversible?” with great
interest, however there are several factors that should be discussed.[1]
First, the only subjects with left ventricular posterior wall measurements
beyond normal limits were the users, which were only slightly enlarged
>11.4 mm. We previously reported on the occurrence of left ventricular
posterior wall thickening up to 13 mm in elite drug-free bodybuilders.[2]
In addition, several of the ex-users had a history of growth hormone use
which is known to directly stimulate myocardial growth.[3] One must
question the ex-users left ventricular dimensions upon cessation of
anabolic steroids. Is it possible that myocardium and skeletal muscle mass
are not linearly related in the rate of atrophy? In addition, the ex-users
are still training and could be utilizing the same intensity, as when on
anabolic steroids, thus creating enough of a pressor response to blunt
myocardial atrophy.[4] As physicians we must also understand that not all
anabolic agents have the same physiological effects. Specifically,
anabolic steroids are a class of compounds that are thought to each bind
to the androgen receptor, however, the molecular structure of each
compound varies and even small alterations can induce different
physiological and biochemical responses. For example, when looking at
three of the injectable oil-based testosterones; enanthate, propionate and
cypionate, we found that polycythemia was induced consistently in subjects
abusing enanthate versus propionate or cypionate, despite almost having
near identical molecular structures.[5] While we understand and accept
the inability to control for self-reported abuse of unknown quality and
quantity of medications, we must also not assume that the subjects are
taking the same medications. Serum testosterone levels would have been
beneficial to have measured on each subject. Could some of the ex-users
have still been using or could there levels still be elevated? Lastly, we
disagree with the comment that training regimens do not differ among the
groups, it is obvious from the performance data that the weightlifters had
significantly (p<_0.001 worse="worse" performance="performance" in="in" cardiovascular="cardiovascular" exercise="exercise" and="and" the="the" anthropomorphic="anthropomorphic" data="data" shows="shows" much="much" higher="higher" average="average" of="of" bodyfat="bodyfat" weightlifters.="weightlifters." this="this" study="study" offered="offered" useful="useful" information="information" for="for" future="future" studies="studies" such="such" as="as" longitudinal="longitudinal" on="on" individual="individual" athletes="athletes" off="off" anabolic="anabolic" steroids="steroids" however="however" we="we" feel="feel" did="did" not="not" clearly="clearly" implicate="implicate" a="a" cause="cause" concentric="concentric" left="left" ventricular="ventricular" hypertrophy="hypertrophy" ex-="ex-" users="users" when="when" considering="considering" multiple="multiple" aforementioned="aforementioned" uncontrolled="uncontrolled" variables.="variables." p="p"/>References
1. Urhausen A, Albers T, Kindermann W. Are the cardiac effects of
anabolic steroid abuse in strength athletes reversible? Heart 2004;90:496-
501.
2. Dickerman RD, Schaller F, McConathy WJ. Left ventricular wall
thickening does occur in elite power athletes with or without anabolic
steroid Use. Cardiology 1998;90:145-148.
3. Saca L. Growth hormone: a new therapy for heart failure?
Baillieres Clin Endocrinol Metab. 1998;12:217-31.
4. McDougall JD, Tuxen D, Sale DG, Moroz JR, Sutton JR. Arterial
pressure response to heavy resistance exercise. J Appl Physiol 1985;58:785
-789.
5. Dickerman RD, Pertusi R, Miller J, Zachariah NY.Androgen-induced
erythrocytosis: is it erythropoietin? Am J Hematol 1999;61:154-155.
Departments of Surgery and Medicine, University of North Texas Health
Science Center, Fort Worth, TX, USA, 76107-2699
We read with great interest the paper by Ismail et al. on the risk
factors for nonfatal myocardial infarction (AMI) in young South Asians
adults.[1]
The authors acknowledged they did not address two important risk factors,
which we believe were significant omissions.
1. The absence of analysis of AMI triggering events. In
the West, 20-30% of AMI are triggered by...
We read with great interest the paper by Ismail et al. on the risk
factors for nonfatal myocardial infarction (AMI) in young South Asians
adults.[1]
The authors acknowledged they did not address two important risk factors,
which we believe were significant omissions.
1. The absence of analysis of AMI triggering events. In
the West, 20-30% of AMI are triggered by extreme emotional or physical
stress, such as anger, fear, death of significant person, and snow
shoveling.[2,3] The study by Ismail et al. could have been an excellent
chance to study this issue in South Asia. In Jordan, a geographically and
socio-economically different area form the West and South Asia, the Jordan
Cardiology Collaborating Cardiology (JCC) Group is currently studying such
triggers in patients with ST-segment elevation AMI. Preliminary data
indicate the presence of a trigger, in up to 50% of cases enrolled so far.[4] 2. Only serum total cholesterol was analyzed. The high
prevalence of low HDL-cholesterol (57% and 47% of men) in Iran [5] and the
Middle East [6], respectively, is further complicated by high prevalence
of diabetes and cigarette smoking. Do the authors have data on prevalence
of low HDL-C in the population they studied, and what percentage of those
had low LDL-C? Clearly, his carries an important implications on using
statins or other lipid lowering agents depending on lipid profile not just
total cholesterol.
References
1. Ismail J, Jafar TH, Jafary FH, et al. Risk factors
for non-fatal myocardial infarction in young South Asian adults. Heart
2004;90:259-263
2. Mittleman MA, Maclure M, Sherwood JB, et al. for
the Determinants of Myocardial Infarction Onset Study Investigators.
Triggering of Acute Myocardial Infarction Onset by Episodes of Anger
Circulation. 1995;92:1720-1725
3. Hammoudeh AJ, Tabbalat R, Al-Tarawneh H, Al-
Harassis,et al. for the Jordan Cardiology Collaborating Cardiology (JCC)
Group. Bulletin of the Jordan lipid and Hypertension Society 2004;6:4
4. Haft JI. Coronary plaque rupture in acute coronary
syndromes triggered by snow shoveling (letter). New Engl J Med 1996; 335:
2001.
5. Rafiei M, Boshtam M, Sarraf-Zadegan N. Lipid
profiles in the Isfahan population: an Isfahan cardiovascular disease risk
factor assay, 1994. Eastern Med Health J 1999;5:766-77
6. Hammoudeh AJ. Adverse effects on serum lipid
profile and coronary artery disease severity due to the coexistence of
diabetes mellitus and cigarette smoking in Jordan. Leb Med J 2003;51
(suppl):36.
The commentaries of Dr CF George are very interesting since they
reveal the cultural gap in the redaction of death certificates on both
sides of the Channel. The analysis of death certificates is a very
relevant tool in general epidemiology and it seems that the tradition in
anglo-saxon epidemiology has focused the physicians’ attention on a
thorough and scrupulous redaction of the causes of death. As...
The commentaries of Dr CF George are very interesting since they
reveal the cultural gap in the redaction of death certificates on both
sides of the Channel. The analysis of death certificates is a very
relevant tool in general epidemiology and it seems that the tradition in
anglo-saxon epidemiology has focused the physicians’ attention on a
thorough and scrupulous redaction of the causes of death. As presented in
table 1,[1] coronary heart disease (CHD) mortality rates assessed by
death certificates or by the data provided by the MONICA Project are
similar in Scotland or in Ireland.
In France, the situation is different:
in Lille, CHD mortality is 1.9 higher according to the MONICA Project, 1.8
in Strasbourg and 1.7 in Toulouse when compared to the official data. To
compare incidence and mortality rates between countries, the MONICA
standardised mortality and incidence data collection and processing. So,
data in table 1 concerning CHD mortality or coronary events can be
compared when they take into account the data validated by the MONICA
Project. In other terms, raw data are no longer taken into account in the
comparison of data provided by the validated study of causes of death and
coronary events according to the MONICA Project. For Toulouse, these long-
term data have been recently published.[2,3] Thus, it seems obvious that
CHD mortality in France is much lower than the mortality observed in
Northern European countries.
The first part of the definition of the French Paradox is therefore
validated on an international level. Death certificates must not be
directly analysed but must be submitted to supplementary analysis
concerning the circumstances of death and validated by a thorough
investigation carried out for each death certificate.
As mentioned in the second part of the commentary of Dr CF George, the
French Paradox is the observation of epidemiological data on a population
level but does not provide any information on the origin of the causes
responsible for such a relative protection of the French population
against CHD. This is what we tried to discuss in this review (1). In this
article, we have shown that new perspectives accounting for the relative
protection of the French and some other populations are available. As for
the statement asserting that this lower CHD mortality could be due to an
overestimate of other causes, it should be discussed more thoroughly and
would mean more complex analyses to validate other causes. This was not
part of our work. As demonstrated by many observational studies, we hope
that the regular consumption of fruit and vegetables and the moderate
intake of red wine have a beneficial effect on other pathologies.
References
1. Ferrières J. The French Paradox: lessons for other countries. Heart
2004;90(1):107-11.
2. Ferrières J, Cambou JP, Ruidavets JB, Pous J. Trends in acute
myocardial infarction prognosis and treatment in Southwestern France
between 1985 and 1990 (The MONICA Project-Toulouse). Am J Cardiol
1995;75:1202-5.
3. Marques-Vidal P, Ruidavets JB, Cambou JP, Ferrières J. Impact of
incidence, recurrence and case-fatality rates of myocardial infarction in
coronary heart disease mortality in Southwestern France, 1985-1993. Heart
2000;84:171-5.
Hayashi et al.[1] report two cases of acute myocardial infarction
caused by thrombotic occlusion at a stent site two years after stenting.
This report further supports the concept that there is a continuous risk
for late stent thrombosis, a concept we described in our study of 1191
nonbrachytherapy patients undergoing coronary stenting and followed for 1
year after stent placement.[2] We...
Hayashi et al.[1] report two cases of acute myocardial infarction
caused by thrombotic occlusion at a stent site two years after stenting.
This report further supports the concept that there is a continuous risk
for late stent thrombosis, a concept we described in our study of 1191
nonbrachytherapy patients undergoing coronary stenting and followed for 1
year after stent placement.[2] We found that the incidence of late stent
thrombisis (stent thrombosis > 30 days) was 0.76% (9 out of 1191
patients), almost equal to that of subacute stent thrombosis 0.92% 2.
Hayashi’s elegant description and pictures adds to our knowledge of this
subject.
References
1. Hayashi T, Kimura A, Ishikawa K. Acute myocardial infarction
caused by thrombotic occlusion at a stent site two years after
conventional stent implantation. Heart 2004; 90:e26.
2. Wang FW, Stouffer GA, Waxman S, Uretsky BF. Late coronary stent
thrombosis: early vs. late stent thrombosis in the stent era. Cathet
Cardiovasc Intervent 2002; 55:142-147.
Dear Editor
We have reported that duodenal mucosa rapidly disposes of both acid and alkali in vitro; neither property being altered by gassing with N2 while iodoacetate was in the perfusing solutions. While acid disposal progressively decreased with time in complementary experiments with in vitro gut sacs, with in vivo gut sacs no fatigue was evident raising the possibility of an active component in the properti...
Dear Editor
I read with great interest the published study by Urhausen et al. [1] It is known that anabolic steroid use in athletes has become a major medical issue. Although Urhausen et al. found that left ventricular wall thickness related to fat-free body mass did not differ between users and ex-users, Sachtleben et al. [2] previously reported that the parameters of left ventricular thickness showed si...
Dear Editor
La Vecchia et al. [1] considered increased cardiac troponin on admission to be the strongest independent predictor of mortality in acute pulmonary embolism. They attributed the increased troponin to right ventricular involvement, because they excluded patients with known or prior coronary artery disease in their study. The criteria they used for exclusion were documented angina, previous myocardial...
Dear Editor
We read with great interest the article by Jaster et al. [1] dealing with the failure by aspirin and clopidogrel to inhibit platelet activation during vascular brachytherapy after percutaneous coronary intervention, which is responsible for a higher risk of stent thrombosis. With respect to the above, we would like to inform about some findings dealing with this issue.
Platelet aggre...
Dear Editor
The induction of ischaemia is accompanied by a fall in tissue pH. The fall is probably due to unreversed ATP hydrolysis rather than the accumulation of lactate. Stochiometric examination reveals that there is no net gain of protons during anaerobic glycolysis. Furthermore the degree of acidosis induced is not reduced by inhibiting glycolysis with iodoacetate and oxidative phosphorylation with KCN and ca...
Dear Editor
We were interested to read Dr Thorne’s article on pregnancy in heart disease and have been developing our service locally for pregnancy in congenital heart disease.[1] We have been particularly concerned with the counselling and management of women following Mustard procedure as many of this unique group are now of child bearing age and there is little data as to their pregnancy outcome.[2]
We...
Dear Editor
I read the article by Urhausen et al. “Are the cardiac effects of anabolic steroid abuse in strength athletes reversible?” with great interest, however there are several factors that should be discussed.[1]
First, the only subjects with left ventricular posterior wall measurements beyond normal limits were the users, which were only slightly enlarged >11.4 mm. We previously reported on...
Dear Editor
We read with great interest the paper by Ismail et al. on the risk factors for nonfatal myocardial infarction (AMI) in young South Asians adults.[1]
The authors acknowledged they did not address two important risk factors, which we believe were significant omissions.
1. The absence of analysis of AMI triggering events. In the West, 20-30% of AMI are triggered by...
Dear Editor
The commentaries of Dr CF George are very interesting since they reveal the cultural gap in the redaction of death certificates on both sides of the Channel. The analysis of death certificates is a very relevant tool in general epidemiology and it seems that the tradition in anglo-saxon epidemiology has focused the physicians’ attention on a thorough and scrupulous redaction of the causes of death. As...
Dear Editor
Hayashi et al.[1] report two cases of acute myocardial infarction caused by thrombotic occlusion at a stent site two years after stenting.
This report further supports the concept that there is a continuous risk for late stent thrombosis, a concept we described in our study of 1191 nonbrachytherapy patients undergoing coronary stenting and followed for 1 year after stent placement.[2] We...
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