Normal Coronary Circulation Research Articles

Cardiac implications of amlodipine-dantrolene combinations.

Cardiac disorders, cardiac arrest and ventricular fibrillation in the most severe cases, have been observed after the administration of dantrolene to patients treated by verapamil for coronary artery disease. This study was designed to examine the interaction of dantrolene with amlodipine, a dihydropyridine. In 12 anaesthetized, open-chest pigs, the effects of the interaction have been studied on heart rate, atrioventricular conduction, monophasic action potential duration, intraventricular conduction time, left ventricular dP/dt max and mean blood pressure. The study was performed with normal coronary circulation and ischaemia of a large area of the left ventricule, obtained by complete occlusion of the left anterior descending coronary artery near its origin, under pacing at a constant high rate, 180 beats.min-1. The drugs were injected iv, amlodipine 0.4 mg.kg-1 first and dantrolene 3.0 mg.kg-1 20 min later in six animals and the order was reversed in the other animals. Sinus rate and atrioventricular conduction were not affected by amlodipine, but were slowed by dantrolene added (145 +/- 9 to 131 +/- 7 beats.min-1, P < 0.01 and 150 +/- 15 to 180 +/- 20 msec, P < 0.01). In contrast, amlodipine or amlodipine plus dantrolene did not change MAP duration or conduction time in the normal heart. Similarly, they did not alter the maximal variations due to ischaemia, but delayed them, while prolonging the time to onset of fibrillation (111 +/- 8 to 343 +/- 33 sec. P < 0.001 with amlodipine alone, 289 +/- 11 to 323 +/- 16 sec, P < 0.05 with dantrolene). Left ventricular dP/dt max was lowered from 1670 +/- 86 to 1532 +/- 50 mmHg.sec-1 (P < 0.001) and mean blood pressure from 79 +/- 4 to 70 +/- 3 mmHg (P < 0.01) by amlodipine, but dantrolene did not enhance and even counteracted these effects. Finally, potassium plasma concentration did not increase above 5.1 +/- 0.2 mmol.L-1 under the dual influence of amlodipine and dantrolene. In usual clinical doses, dantrolene may be safely administered concurrently with amlodipine.

Digital Angiographic Impulse Response Analysis of Myocardial Perfusion: Influence of Heart Rate and Blood Pressure Changes on Microcirculatory Transit Time Measurement in the Normal Canine Coronary Circulation

The study describes the effect of acute changes in aortic blood pressure and heart rate in the intact normal canine coronary circulation on digital angiographic measurements of the mean transit time of the microcirculation compartment and on direct flow meter measurement of resting and maximal hyperemic coronary blood flow. The mean transit time of the radiographic contrast material through the normal coronary circulation was calculated in 20 dogs by the impulse response analysis from serial digital coronary angiograms under systematically changed blood pressure and heart rate conditions. The mean aortic blood pressure (MAP) was controlled by the inflation of a balloon in the descending aorta (70-150 mm Hg). The heart rate was altered by atrial pacing (90, 120, and 150/min). The mean transit times ( T μ) of contrast material across the myocardial microcirculation which had been recently shown to correlate with coronary flow reserve (CFR) in stenosed arteries in the canine model were calculated under resting and hyperemic flow conditions from 428 selective coronary anglograms after a hand-injected contrast bolus. T μ was found to be heart rate independent. T -1 μ was linearly correlated with MAP ( r - 0.7). There was no difference in T μ under resting and hyperemic flow conditions at comparable MAP. The corresponding distribution volume ( V μ) of the microcirculation was calculated as the product of the mean transit time T μ and the measured coronary blood flow. Under resting flow conditions, V μ decreased with rising MAP. Furthermore, V μ, increased with rising heart rate. V μ was constant during blood pressure or heart rate changes under hyperemic flow conditions. The data suggest that CFR whether by direct measurements of flow or by radiographic assessment of contrast material kinetics should be standardized with respect to hemodynamic conditions of heart rate and MAP.

Limit to cardiac compensation during acute isovolemic hemodilution: influence of coronary stenosis.

We assessed limit to cardiac compensation during isovolemic hemodilution (HD) in 14 anesthetized dogs. Radioactive microspheres were used to evaluate myocardial blood flow (MBF) and its transmural distribution (endo/epi). Myocardial O2 consumption (MVO2) and percent lactate extraction were determined. Coronary vasodilator reserve was assessed from reactive hyperemic responses. Dogs were divided into group 1, with intact left anterior descending coronary artery (LAD), and group 2, with critical stenosis of LAD. Measurements were obtained at baseline and during graded HD (Hespan) until cardiac failure (CF). CF occurred at lower hematocrit in group 1 compared with group 2 (9 +/- 1 vs. 17 +/- 1%). In group 1, MBF increased during HD to maintain MVO2 constant; increases in MBF were transmurally uniform until CF, when decreased endo/epi and lactate production suggested subendocardial ischemia. Coronary vasodilator reserve decreased progressively during HD and was absent at CF. In group 2, stenotic LAD demonstrated constant MBF (resulting in decreased MVO2) during HD. At CF, these responses along with reduced endo/epi and lactate production indicated local myocardial ischemia. We conclude that 1) with normal coronary circulation, cardiac function was well maintained over a wide range of hematocrits because increases in MBF were transmurally uniform and sufficient to maintain myocardial oxygenation: CF occurred during extreme HD when MBF became maldistributed, resulting in subendocardial ischemia; 2) critical coronary stenosis impaired coronary vascular adjustment to HD and reduced significantly tolerance of left ventricle to HD; and 3) present findings underscore the importance of recruitment of coronary vasodilator reserve in preserving total and regional myocardial oxygenation during HD.

Influence of Ketanserin on Regional Myocardial Blood Flow After Myocardial Infarction in Baboons

Serotonin (5-hydroxytryptamine, 5-HT) mediates vasoconstriction and vasodilation in normal coronary circulation of various animal species. In the presence of coronary artery disease, serotonin may inhibit coronary collateral formation and stimulate predominantly vasoconstriction. We tested the effect of ketanserin, a selective 5-HT2 receptor antagonist and platelet aggregation inhibitor, on ischemic myocardium blood flow (BF) and collateral formation after coronary artery occlusion in primates. Fifteen baboons were subjected to left anterior descending coronary artery (LAD) ligation and thrombus formation. Hemodynamics and regional myocardial blood flow (RMBF) (microsphere technique) were measured before and 45 min and 1 week after coronary artery occlusion. There was no significant difference in the hemodynamic measurements, gross infarct size, or infarct-ischemic zone MBF in the experimental group (ketanserin 1 mg/kg daily, n = 9) as compared with the control group (injectable water, n = 6). Both groups had a significant increase in BF ratio of infarct-ischemic/normal myocardium at 1 week as compared with shortly after coronary occlusion. Thus, selective 5-HT2 receptor blockade has neither an adverse nor a protective effect on myocardial infarct resulting from acute thrombotic coronary occlusion in baboons.

Role of alpha 2-adrenoceptors in normal and atherosclerotic human coronary circulation.

Experimental studies on the effects of alpha 2-adrenoceptors on regional coronary blood flow in normal and ischemic myocardium are highly controversial. A beneficial effect on regional ischemic myocardium has been demonstrated in different animal preparations with either alpha 2-adrenoceptor blockade or stimulation. Animal studies also demonstrated that postsynaptic alpha 2-adrenoceptors mediate vasoconstriction in coronary and femoral vascular beds. The aims of the study were 1) to investigate the effects of regional alpha 2-adrenoceptor stimulation on regional coronary blood flow in subjects with angiographically normal coronary arteries, 2) to assess the effect of alpha 2-adrenoceptor blockade on coronary circulation in control subjects, and 3) to examine the influence of atherosclerosis on coronary blood flow response to alpha 2-adrenoceptor blockade. The effect of regional administration of BHT 933 (a selective alpha 2-adrenoceptor agonist) was studied in eight subjects with angiographically normal coronary arteries. The coronary blood flow velocity was measured using a subselective intracoronary 3F Doppler catheter and coronary diameter by quantitative coronary angiography. BHT 933 induced a reduction in coronary artery diameter from 2.5 +/- 0.6 mm to 1.8 +/- 0.4 mm (p less than 0.05) as well as in coronary blood flow velocity (from 6.4 +/- 0.9 cm/sec to 4.6 +/- 1.9 cm/sec, p less than 0.01). In some subjects, ST segment abnormalities occurred. In patients with angiographically normal coronary arteries (n = 6), the regional infusion of a selective alpha 2-adrenoceptor blocking agent after beta-blockade did not change coronary diameter or coronary blood flow velocity. In contrast, in patients with significant coronary stenoses (n = 6), regional infusion of an alpha 2-adrenoceptor blocking agent reduced regional coronary artery diameter (from 2.3 +/- 0.5 mm to 2.1 +/- 0.6 mm, p less than 0.01) as well as coronary blood flow velocity (from 5.8 +/- 0.8 cm/sec to 3.7 +/- 0.6 cm/sec, p less than 0.05); in addition, alpha 2-adrenoceptor blockade significantly increased coronary sinus plasma norepinephrine levels (from 300 +/- 144 pg/ml to 429 +/- 207 pg/ml, p less than 0.01). The selective in vivo stimulation of alpha 2-adrenoceptors produces a reduction in coronary blood flow and diameter in humans with angiographically normal coronary arteries. alpha 2-Adrenergic blockade does not change coronary blood flow in subjects with angiographically normal coronary arteries (suggesting no resting alpha 2-adrenergic vasoconstrictor tone), whereas in patients with coronary artery stenosis, regional coronary blood flow decreases after alpha 2-receptor blockade. Finally, our data also suggest that alpha 2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the human heart.

Mechanisms of Acute Myocardial Ischemia: Pathophysiology of Myocardial Blood Flow

Summary Myocardial ischemia results from a decline in the oxygen supply-and-demand ratio. The consequences of ischemia range from metabolic disturbances, detectable only by research techniques, to sudden death. The heart is unique in that it must generate pressure for its own perfusion. This results in complex interrelationships between the factors determining myocardial oxygen supply and demand. In the presence of a coronary stenosis, the effects of hemodynamic changes become even more difficult to predict. An understanding of the physiology of the normal and diseased coronary circulation helps the anesthesiologist protect the patient with coronary artery disease from cardiac morbidity.

Cardiovascular Effects of Elgodipine in Conscious Pigs with a Normal Coronary Circulation and in Conscious Pigs witha Healed Myocardial Infarction

The cardiovascular effects of the phenyldihydropyridine derivative elgodipine (0.3, 1, 3, 10, and 30 microgram/kg/min) were studied in normal conscious pigs and in pigs with chronic left ventricular dysfunction (LVD, caused by coronary artery occlusion) without and after beta-adrenoceptor blockade with propranolol (0.5 mg/kg + 0.5 mg/kg/h). In normal pigs, elgodipine increased cardiac output from 2.57 +/- 0.09 to 5.21 +/- 0.24 L/min (p less than 0.05) as a result of a doubling of the heart rate. Mean arterial blood pressure decreased from 94 +/- 2 to 76 +/- 3 mm Hg (p less than 0.05) as a result of a decrease in systemic vascular resistance. Left ventricular (LV) dP/dtmax increased (by up to 78 +/- 9%), but left ventricular end-diastolic pressure (LVEDP) remained unchanged. After propranolol administration elgodipine did not increase LV dP/dtmax, and the increase in heart rate was attenuated, resulting in a smaller increase in cardiac output (from 2.11 +/- 0.13 to 3.09 +/- 0.23 L/min, p less than 0.05), but an unchanged vasodilator response. In pigs with LVD, elgodipine increased cardiac output and LV dP/dtmax less than in normal animals, but the vasodilator response was not affected. LVEDP decreased from 14.6 +/- 1.6 to 11.7 +/- 2.5 mm Hg (p less than 0.05). In animals with LVD, propranolol caused a more severe depression of systemic hemodynamics, but did not modify the cardiovascular responses to elgodipine. Its cardiovascular profile suggests that elgodipine may not only be useful in the treatment of cardiovascular disorders for which other dihydropyridines are already in use, but also in mild chronic heart failure.

Enhanced coronary vasoconstrictor responses to 5‐hydroxytryptamine in the presence of a coronary artery stenosis in anaesthetized dogs

1. In the anaesthetized dog, left circumflex coronary artery blood flow and external diameter were measured and the vascular responses to an injection of 5-hydroxytryptamine (5-HT, 0.02-2 micrograms kg-1) assessed, before and after a screw clamp had been placed on the artery to produce a severe stenosis. 2. In the normal coronary circulation, intra-coronary (i.c.) injection of 5-HT increased coronary blood flow (CBF) but decreased the external diameter of the large coronary artery (CD), without affecting systemic mean arterial pressure or heart rate. 3. In the normal coronary circulation, the 5-HT-induced increases in CBF were unaffected by blockade of 5-HT2-receptors with ketanserin (0.1 mg kg-1 i.c.) but were significantly attenuated by blockade of 5-HT1-like receptors with methysergide (0.1 mg kg-1 i.c.). 4. In the presence of a severe stenosis, the increase in CBF produced by 5-HT was markedly attenuated and a secondary decrease in CBF was revealed. The stenosis also caused a marked enhancement of the 5-HT-induced constriction of the large artery, such that the reduction of the CD was approximately doubled at all doses of 5-HT tested. The enhanced 5-HT-induced reduction in CD was similar with placement of the stenosis either proximal or distal to the site of diameter measurement. 5. In the presence of the stenosis, blockade of 5-HT 2-receptors with ketanserin (0.1 mg kg-1 i.c.) significantly attenuated the 5-HT-induced decreases in CD and CBF. 6. These results demonstrate that, in the anaesthetized dog, placement of a severe, flow-limiting stenosis enhances 5-HT-induced constriction of the large coronary arteries and reveals a reduction in coronary blood flow. These observations support suggestions that, in the presence of coronary artery disease, 5-HT could contribute to reductions in coronary blood flow leading to myocardial ischaemia.

Myocardial Blood Flow and Oxygen Consumption during Isovolemic Hemodilution Alone and in Combination with Adenosine-Induced Controlled Hypotension

Recent reports have proposed combining isovolemic hemodilution and controlled hypotension to limit blood loss during surgery. Before such a technique can be considered for clinical use, it must be demonstrated that it does not endanger maintenance of adequate myocardial oxygenation. Accordingly, measurements of left ventricular myocardial blood flow and oxygen consumption were obtained during isovolemic hemodilution alone and in combination with adenosine-induced controlled hypotension in ten pentobarbital-anesthetized, open chest dogs with normal coronary circulation. Hemodilution to a hematocrit of 21.7% was produced by isovolemic exchange of whole blood for 5% dextran. In the presence of hemodilution, adenosine was infused intravenously at a rate sufficient to decrease mean aortic pressure to 51 mm Hg. Myocardial blood flow was measured with radioactive microspheres and used to calculate global left ventricular myocardial oxygen consumption and oxygen supply. Hemodilution alone increased aortic blood flow (+43%) but had no effect on aortic pressure, left atrial pressure, heart rate, or left ventricular dP/dtmax; an increase in myocardial blood flow (+130%) maintained oxygen supply and consumption at the baseline level. Adenosine-induced hypotension during hemodilution decreased heart rate (-35%), left ventricular dP/dt max (-28%), and aortic blood flow (-14%). These systemic responses were accompanied by reduced myocardial oxygen consumption (-29%) and increased myocardial blood flow (+54%) and myocardial oxygen supply (+72%). These latter effects resulted in reduction in the coronary arteriovenous oxygen content difference and in an attendant rise in coronary sinus Po2 (+66%), which are signs of luxuriant myocardial perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties

Intravenous infusions of 0.01–0.1 mg · kg −1 · min −1 of pimobendan, a benzimidazole-pyridazinone derivative in pigs with normal coronary circulation caused dose-dependent changes in heart rate (10–35%), left ventricular systolic pressure (−5 to −45%), left ventricular filling pressure (−20 to −40%) but had only a minor effect on the maximum rate of rise of left ventricular pressure (max LVdP/dt; 10–20%). The decrease in mean arterial blood pressure was primarily due to systemic vasodilation; peripheral resistance and cardiac output decreased by up to 40 and 14%, respectively. Vasodilation occurred in several vascular beds, but was particularly pronounced in the adrenals, stomach, small intestine and myocardium. Although the increase in myocardial blood flow favoured the epicardium, vascular conductance in both the endo- and epicardial layers was significantly increased. Myocardial O 2 consumption (MVO 2) was not affected despite the increase in heart rate. Bolus injections of 0.1–0.5 mg · kg −1 pimobendan produced similar changes in all haemodynamic variables, except max LVdP/dt which now increased by 30–70%. As in the infusion experiments, cardiac output tended to decrease due to a pronounced reduction in ventricular preload probably as a result of venodilation and the consequent reduction in cardiac filling. However, in animals where max LVdP/dt and cardiac output were reduced and pre- and/or after-load were increased by partial occlusion of the left anterior descending coronary artery, pimobendan clearly increased both max LVdP/dt and cardiac output. Pretreatment with propranolol did not modify any of the cardiovascular responses to pimobendan, thereby excluding the involvement of a β-adrenoceptor mechanism. Pimobendan is thus a compound with vasodilator and positive inotropic properties that improves cardiac output in animals with severe myocardial ischaemia. The finding that the mild tachycardia caused by pimobendan was not accompanied by an increase in MVO 2 warrants investigation to evaluate its usefulness in the treatment of heart failure.

Adenosine's role in regulating basal coronary arteriolar tone.

This study examined the role of adenosine in regulating coronary arteriolar tone under basal conditions in the normal coronary circulation. Measurements of hemodynamics and flow (microspheres) were made in eight closed-chest, sedated pigs at 1) control and 2) after 10 min of infusion of adenosine deaminase (ADA, 10 U X kg-1 X min-1) into the left anterior descending (LAD) coronary artery. Heart rate was held constant by atrial pacing. Transmural flow in the distal LAD zone did not change versus control (1.81 +/- 0.36) with ADA (1.78 +/- 0.46). However, in comparison with control the distal LAD:circumflex zone transmural flow ratio (0.96 +/- 0.04) declined (P less than 0.01) during ADA infusion (0.93 +/- 0.04). Similarly, the distal LAD:circumflex zone transmural flow resistance ratio increased significantly (P less than 0.01) versus control (1.04 +/- 0.05) in response to intracoronary ADA infusion (1.08 +/- 0.04). Regional myocardial oxygen consumption in the distal LAD zone did not change versus control (16.9 +/- 3.3 3.3 ml X min-1 X 100 g-1) during ADA (16.9 +/- 4.5). Additional studies in 15 open-chest swine given intracoronary infusion of ADA demonstrated that 1) the enzyme penetrates the interstitial fluid (ISF) and 2) attains ISF levels which are adequate to reduce basal adenosine concentration 10 fold even if substantial increase in adenosine production occurs in response to ADA. Thus, since destruction of adenosine by ADA caused only very modest relative reduction in regional flow, it is likely that the nucleoside plays only a limited role in regulation of arteriolar tone under basal conditions in the normal coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiology of Coronary and Myocardial Function in Angina Pectoris: Important Aspects for Drug Treatment

Knowledge of ischaemia and its consequences in man has been considerably expanded during the last two decades. This was made possibly mainly through the development of new techniques such as coronary and left ventricular angiography(2), and by various methods of assessing regional coronary blood flow(3) and perfusion(4) in man, especially those employing isotopes and computer-assisted devices to study regional wall motion(5). All these techniques allow analysis of both the anatomy and the function of the coronary system and the left ventricle in detail which was never achieved before. These advances, however, also revealed the great complexity of the physiologic and pathophysiologic factors influencing the human coronary circulation in new dimensions. At the same time, treatment of ischaemia entered a new phase; two new invasive methods, bypass surgery(6) and coronary angioplasty(7) were successfully introduced, as well as new classes of antianginal drugs such as beta-blocking agents(8,9) and, in the last decade, the calcium antagonists(10,11) The following review discusses some of the most important and more recent aspects of the normal and abnormal coronary circulation in man, especially those events which play an important role in today's preventive drug treatment of ischaemia.

Exercise testing in suspected coronary artery disease

1. 1. The interpretation and selection of exercise tests depends on the pretest probability of CAD. 2. 2. Imperfect tests (like exercise tests) provide probability estimates, not definite statements (such as “the patient has CAD” or “the patient does not have CAD”). 3. 3. In patients with a low pretest probability of CAD (asymptomatic persons or men and women with nonanginal chest pain), abnormal exercise test results provide probability estimates that are much too low to conclude that the patient has CAD. 4. 4. In patients with anginal pain and normal exercise tests, the probability of CAD is too high to conclude that the patient has a normal coronary circulation. Exercise tests are not useful for trying to rule out CAD in patients with anginal pain. 5. 5. In patients with an intermediate pretest probability of CAD (men and women with atypical angina and women with typical angina), abnormal exercise tests (particularly the myocardial scintiscan) provide probability estimates that are high enough to justify starting treatment for CAD. Exercise tests are most useful in this group, a conclusion that has been reached by other methods of analysis. 67 6. 6. The myocardial scintiscan is much more useful than the exercise ECG in women. 7. 7. When CAD is strongly suspected, exercise tests have relatively little diagnostic value but may be useful for prognosis. However, clinical evidence of poor ventricular function may alone suffice to select patients with angina pectoris for coronary arteriography. Conversely, when clinical indicators of congestive heart failure are absent, the prognosis in chronic stable angina is so favorable that any further testing may be unnecessary. 8. 8. Screening asymptomatic persons for CAD is a very low yield practice. Patients who have no cardiac risk factors (hypercholesterolemia, family history of CAD, cigarette smoking, and hypertension) are at especially low risk of a primary cardiac event. 9. 9. Older men with stable typical angina are particularly likely to have left main coronary artery stenosis or three-vessel disease with poor ventricular function. The exercise ECG can identify groups of older men with a relatively high risk of having left main coronary artery stenosis. 10. 10. Physicians should be cautious when applying these recommendations to a primary care practice. The foregoing analysis is based on data obtained from patients who had been selected for coronary arteriography. There are two principal effects of biased selection of study patients: • • The pretest probability of CAD in clinical subgroups is probably lower than as shown here. The effect of this selection bias is to reduce the probability of CAD when exercise tests are abnormal and to overestimate the yield of an aggressive diagnostic approach. • • If the test performance of exercise tests could be measured in primary care practice, the sensitivity would probably be lower and the specificity higher than as shown here. Therefore, in primary care practice, the probability of disease for both normal and abnormal test results is likely to be higher than as shown here. When interpreting an abnormal test result, these two sources of bias have opposite effects and may partially offset one another.

Spontaneous complete closure of a congenital coronary artery fistula

The first documentation is reported of spontaneous closure of a coronary artery to right ventricle fistula that was demonstrated initially in a 14 month old boy. Over a 4 year period after diagnosis, the characteristic continuous murmur gradually disappeared. When the patient was 5 1/2 years of age, selective coronary arteriography showed normal coronary vessels and circulation. Six other cases of coronary fistula observed during the past 10 years are also reviewed. This study supports the rationale for clinical follow-up rather than obligatory surgical intervention in asymptomatic patients with a small shunt who have no evidence of myocardial dysfunction.

Differential effects of Renografin-76 on the ischemic and nonischemic myocardium

The effects of intracoronary diatrizoate meglumine and diatrizoate sodium (Renografin-76) on regional contraction were examined in the normal coronary circulation and during partial (50 percent) coronary occlusion in 11 dogs using strain and length gauges. Intracoronary injections of Renografin-76 (1.5 cc) (1,690 mosM/liter; 0.19 mEq Na/ml), equiosmolar dextrose solution and 0.19 mEq Na +/ml saline solution were made randomly. Renografin-76 caused a decrease in preejection tension to 87.4 ± 4.3 percent (p < 0.025), total tension to 74.6 ± 3.3 percent (p < 0.01) and ejection tension to 11.9 ± 12.6 percent (p < 0.001) of control value. Segment length increased to 106.7 ± 7.3 percent of control value. These changes lasted only 12 ± 2 (range 5 to 20) seconds (mean ± standard error of the mean). During partial coronary occlusion and after injection of Renografin-76, preejection tension decreased from 91.7 ± 6.3 to 53.8 ± 3.9 percent (p < 0.01), total tension from 89.9 ± 5.0 to 59.7 ± 3.5 percent (p < 0.01) and ejection tension from 22.8 ± 8.1 to 17.8 ± 10.9 percent, whereas segment length increased from 112.7 ± 3.7 to 130.7 ± 4.6 percent (p < 0.01) of control value. In contrast to findings in the normal coronary circulation, tension and length changes lasted 54 ± 16 (range 15 to 180) seconds (p < 0.05). The hyperemic response during normal coronary circulation was completely abolished during partial coronary occlusion. Prior administration of nitroglycerin did not shorten the duration of the myocardial depressant effects of Renografin. Injections of equiosmolar dextrose or saline solution produced qualitatively similar but quantitatively less marked changes. Thus, intracoronary Renografin-76 has an accentuated and prolonged depressant effect on the ischemic as compared with the normally perfused myocardium; this effect is not solely due to its hyperosmolarity or sodium concentration.

Ventricular fibrillation during cardiopulmonary bypass.

Changes in ultrastructure after induced ventricular fibrillation were studied in the normothermic and nonhypertrophic canine heart using a transmural myocardial biopsy method. Comparisons were made between subendocardial and subepicardial layers by the quantitative evaluation of ultrastructural changes in mitochondria and glycogen granules. Slight abnormalities characterized by interstitial edema, mitochondrial derangement, contraction bands, swelling of capillary endothelium were demonstrated throughout the myocardium following ventricular fibrillation. The myocardium following ventricular fibrillation did not demonstrate differences in ultrastructure between the subendocardial and subepicardial layers. These pathologic fine structural changes were at least in part reversible. Quantification of ultrastructure showed that mitochondria and glycogen granules were well preserved. It was suggested that the myocardium following ventricular fibrillation may be less affected by the no-reflow phenomenon after restoring normal coronary circulation.

The aortic bodies supplied by coronary arteries in the dog. Their contribution to the hypertensive response that follows serotonin injection.

I assessed the role of the chemoreceptors (aortic bodies) supplied by the coronary arteries in the hypertensive response induced by left atrial injection of (200 microgram serotonin) in adult anesthetized dogs. I compared the pressor response induced by serotonin during normal coronary circulation with that during exclusion of the central coronary segments from which the coronary blood supply to the aortic bodies arises. Exclusion of the central segments reduced the pressor response significantly from the control responses. Exclusion of the coronary blood supply of the aortic bodies resulted in a reduction of the control response of more than 50% in only two of the 21 dogs. I conclude that although the aortic bodies supplied by the coronary arteries play a significant role in the total hypertensive response to injected serotonin, their role usually is not predominant.

Serum antithrombin in coronary-artery disease.

Serum antithrombin activity (AA) was correlated with coronary angiographic findings in 69 patients with documented angina. There was excellent correlation between normal values and normal coronary circulation or only one-vessel stenosis in 30 of 35 patients (86%). When AA was above 90%, 90% of patients (20 of 22) had normal circulation or one-vessel occlusion. In 24 patients AA values were significantly decreased. Coronary angiography in this group revealed three with normal circulation or only one-vessel involvement (10%); 21 of 24 had two or three vessels occluded (90%). The correlation between severe CAD and low AA is probably coincidental to a "triggered" or "turned-on" clotting system. The most practical clinical contribution of AA estimation relates to this capacity to identify angina patients in whom clot-preventive measures (aspirin; dipyridamole; anticoagulants) might prove beneficial.

Effect of nicotine on glyceraldehyde-3-phosphate deydrogenase and lactate/pyruvate ratio of arterial and venous coronary blood in dogs with restricted coronary circulation

Summary The pattern of response of glycoraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate/pyruvate ratio was studied in arterial and venous coronary blood, prior and after infusion of nicotine, in dogs with normal coronary circulation and dogs with coronary obstruction produced by Ameroid rings; at the same time, some of the hemodynamic characteristics of the cardiac activity were evaluated. In dogs with normal coronary circulation, nicotine infusion provokes in the coronary venous blood an increase in GAPDH and a significant increase in the lactate/pyruvate ratio. In animals with chronic ischemia, the nicotine infusion produces a small and inconstant increase in the GAPDH content of the coronary venous blood and no significant modifications in the lactate/pyruvate ratio. In the ischemic myocardium there is evidence of increase in the hexose monophosphate shunt, with decrease in the activity of the glycolytic enzymes and of the tricarboxylic cycle ( Gudbjarnason, et al, 1967 , Gudbjarnason, et al, 1968 , Gudbjarnason, et al, 1968 ). An observation of considerable interest is that the activation of the hexose monophosphate shunt occurs both in the ischemic zone and in that with normal oxygen supply. According to Gudbjarnason et al. (1967) this is explained by the fact that the energy requirements and, above all, the production of ribose-5-phosphate for the synthesis of the proteins necessary for cardiac hypertrophy, are supplied by this metabolic pathway. Glycernaldehyde-3-phosphate dehydrogenase (GAPDH) activity diminishes least among others enzimatic activities with decrease in the ischemic tissue ( Gudbjarnason, et al, 1968 , Gudbjarnason, et al, 1968 ). The importance of this enzyme in the carbohydrate and fat metabolism of the organism in general, and also for the myocardium, is well known: it plays a fundamental role in the activity of the embden-Mayeroff cycle and, indirectly, activates the cycle of the hexose monophosphate shunt in the ischemic tissue ( Gudbjarnason and Bing, 1971 ; Tschopp et al., 1968 ), allowing the conversion of the triose phosphates to acetyl-CoA, facilitating there by also the synthesis of fatty acids. Following up on a series of research initiated by one of us ( Corsini, et al, 1968 , Corsini, 1970 ), the behaviour of GAPDH, parallel with that of lactate/pyruvate ratio, was studied in the arterial and venous coronary blood, prior to and after infusion of nicotine, in dogs with normal coronary circulation, as well as in dogs with coronary circulation restricted by the application of Ameroid. Nicotine was chosen because of its known effects on the cardiocirculatory system (increase of heart rate, blood pressure, stroke volume and reduction in the coronary flow in presence of coronary insufficiency), and also on account of its action on carbohydrate and fat metabolism by stimulating such hormonal systems as the catecholamines and pitressin ( Goodman and Gilman, 1970 ).

The Acute Cardiac Emergency-Diagnosis and Management.

This book, composed of formal papers and selected edited discussions from a program sponsored by the American College of Cardiology, is deceptively titled, containing many more facets of the field of cardiology than is indicated. There are four broad divisions, 27 sections, and 28 authors. Subject material varies from excellent reviews of the basic physiology of arrhythmias and hemodynamics of cardiovascular collapse to prehospital community-planned emergency care. The anatomical-functional diagrams of normal and abnormal coronary circulation, especially of small arteries, and the limited definitions of heart attack as subendocardial, transmural, and sudden death seem overly simplified. Cardiopulmonary resuscitation, probably the most widely applied, important emergency cardiac procedure, is well discussed and indications and broad recommendation of personnel training are presented. The uninitiated or less experienced operator might profit by more explicit details, including diagrams of the techniques and hazards of the procedure. The case history panel discussions are discursive and