Mechanisms and significance of cardiac ischemic pain

We investigated the effect of aminophylline, an antagonist of the adenosine P₁ receptor, on cardiac pain experienced during percutaneous transluminal coronary angioplasty (PTCA).

Adenosine may mediate cardiac pain because the administration of adenosine provokes cardiac pain like angina. However, it is not known whether endogenous adenosine released during myocardial ischemia is responsible for cardiac pain.

This was a single-blind, placebo-controlled randomized study. Of 21 men with stable effort angina with one-vessel coronary artery disease who underwent balloon inflation four times during PTCA, 11 received intravenously administered aminophylline before the fourth balloon inflation and the other 10 were given saline solution. The severity of cardiac pain based on the pain score and ST segment elevation on standard surface and intracoronary electrocardiograms were assessed.

All patients experienced cardiac pain during balloon inflation. Aminophylline significantly prolonged the duration of both the symptom-free interval (from 42 ± 13 to 64 ± 27 s, mean ± SD, p<0.05) and inflation time (from 79 ± 23 to 103 ± 20 s, p<0.05), and it significantly reduced the pain score from 7.6 ± 1.4 to 4.6 ± 2.3 (p<0.01). However, aminophylline did not affect ST segment elevation. Saline solution did not affect any of these variables. Balloon diameter and pressure were not different between the third and the fourth inflation in either group.

Aminophylline significantly reduced the severity of cardiac pain during PTCA without affecting ST segment elevation. These findings suggest that the activation of P₁ receptors by endogenous adenosine may be partially responsible for cardiac pain during ischemia.

Spinal cord stimulation in angina pectoris increases exercise capacity and reduces both anginal attacks and ischemic electrocardiographic signs. This suggests an anti-ischemic action, perhaps through changes in myocardial blood flow. In 9 patients, regional myocardial blood flow was studied with positron emission tomography before and after 6 weeks of spinal cord stimulation, both at rest and during a dipyridamole stress test. Frequency of anginal attacks ana consumption of short-acting nitrates were assessed by patient diaries. Exercise duration and time to angina were measured with treadmill exercise tests. After 6 weeks of stimulation, both frequency of daily anginal attacks and nitrogen consumption decreased (3.7 ± 1.7 vs 1.4 ± 1.0 [p < 0.01] and 2.8 ± 2.2 vs 1.1 ± 1.2 tablets [p = 0.01], respectively); exercise duration and time to angina increased (358 ± 165 vs 493 ± 225 seconds [p < 0.01] and 215 ± 115 vs 349 ± 213 seconds [p = 0.02], respectively); and ST-segment depression during dipyridamole stress testing was reduced (0.17 [0 to 0.5] mV vs 0.09 [0 to 0.2] mV, p = 0.04) (all data mean ± SD). Total resting blood flow remained unchanged (115 ± 29 vs 127 ± 31 ml/min/100 g, p = 0.31), but flow reserve decreased (146 ± 43% vs 122 ± 39%, p = 0.04). The coefficient of variation of flow, representing flow heterogeneity, decreased after treatment, both at rest (20.1 ± 3.8% vs 17.4 ± 2.6%, p = 0.04) and after dipyridamole stress (26.2 ± 4.4% vs 22.9 ± 5.5%, p = 0.02). Thus, spinal cord stimulation is clinically effective due to homogenization of myocardial blood flow. Since flow reserve decreases despite clinical improvement, the dipyridamole effect may be blunted by spinal cord stimulation.

Patients with coronary artery disease (CAD) may develop symptomatic (angina) or asymptomatic (silent) myocardial ischemia. Perioperative myocardial ischemia in CAD patients can occur secondarily due to hemodynamic aberrations or spontaneously, without hemodynamic changes. Proper preoperative evaluation and preparation followed by aggressive perioperative monitoring and treatment may reduce the incidence of life-threatening cardiac events in these patients.

Myocardial ischemia is the event resulting from the insufficient supply of oxygen and nutrients to meet the metabolic demands of the cardiac tissue. Ischemia can be due to a reduction in blood supply or flow, increase in the demand, or usually a combination of both. Ischemia results when blood flow is sufficient for cell life preservation but inadequate for normal physiologic function. Myocardial infarction (MI) results when blood flow is insufficient for cell survival. Ischemia with dysfunction followed by reperfusion before the death of myocardial cells results in stunned myocardium. Chronic low flow states produce hibernating myocardium.⁵⁰ The cellular changes resulting from ischemia or infarction produce electrical and functional alterations that can be observed clinically and by using the available monitors.

An increased incidence of myocardial infarction following surgery was reported by Randall et al in 1930,⁹⁰ Master et al in 1938,⁷⁷ Wroblewski et al in 1952,¹¹⁷ and Topkins et al in 1964.¹¹² The more recent report of Tarhan et al¹⁰⁸ created the impetus for the extensive research that followed. These more recent studies were performed to correlate the relationship of preoperative, intraoperative, and postoperative myocardial ischemia and the development of serious and life-threatening cardiac events such as myocardial infarction, dysrhythmias, cardiac failure, and death in surgical patients. Keats⁴⁵ questioned the conclusions of many of those studies.

Do anesthesia and surgery increase the rate of infarction in patients with cad compared with similar patients not undergoing surgery? What is the precipitating event for the development of myocardial infarction? Keats concluded that perioperative ischemia was predictive of postoperative MI, that ischemia was not related to hemodynamic aberrations except tachycardia, preoperative beta-blocker therapy was beneficial, and there was no difference in the outcome between the types of anesthetic agents or techniques used. He also observed that those patients who manifest ischemic changes would have a higher incidence of perioperative MI.

In this article, some of the important concepts to understand myocardial ischemia and its relevance to anesthesia and surgery leading to ischemia and perioperative cardiac complications are discussed.

Objectives. This study sought to assess the presence and extent of inducible myocardial dysfunction during painful and painless (silent) myocardial ischemia in a homogeneous patient cohort with coronary artery disease and no previous myocardial infarction.

Background. The functional significance of painless versus painful demand-driven ischemia remains controversial, with conflicting results in published reports regarding the amount of myocardium in jeopardy.

Methods. Exercise echocardiography was performed in 89 patients (mean [±SD] age 59.3 ± 8.2 years) with significant coronary artery disease and positive exercise stress test results. Patients were taking no antianginal medications and were classified into painless and painful cohorts after the outcome of a symptom-limited treadmill exercise test. No patients had previous coronary artery bypass surgery. Images were acquired in digital format before and immediately after treadmill exercise testing.

Results. Fifty-eight patients had painful and 31 painless myocardial ischemia. Clinical and demographic characteristics as well as coronary artery anatomy were similar in both groups. Patients with painless ischemia achieved better exercise performance with greater exercise duration (p < 0.001) and higher maximal rate-blood pressure product (p < 0.001) than those with painful ischemia. New wall motion abnormalities were seen in 54 patients (93%) with painful versus 17 (55%) with painless ischemia (p < 0.001). Total ischemic score was greater in patients with painful than in those with painless ischemia (15.9 ± 3.7 vs. 12 ± 1.4, p < 0.001, respectively), with a greater number of ischemic myocardial segments in painful than in painless ischemia (101 [16%] vs. 21 [6%], p < 0.001, respectively).

Conclusions. Patients with painless ischemia frequently have regional myocardial dysfunction on exertion detected by echocardiography, but painful episodes are accompanied by a greater magnitude of myocardial dysfunction.