Periods Of Coronary Occlusion Research Articles

Reduced incidence of intraoperative myocardial infarction during coronary bypass surgery with use of intracoronary shunt technique

Intraoperative myocardial infarction is a recognized complication of aortocoronary bypass surgery. One major cause of such infarction may be interruption of coronary blood flow, particularly in patient with poor coronary collateral circulation. In 30 patients use of an intracoronary shunt made it possible to limit the period of coronary occulusion during graft construction to a few minutes. Use of this shunt was associated with a reduced incidence of intraoperative myocardial infarction (as judged by the appearance of new Q waves) when these patients were compared with 50 patients operated on without this procedure (6 of 50 [12 percent] versus 0 of 30). The incidence of postoperative persistent S-T segment elevation was reduced from 21 of 50 (42 percent) to 5 of 30 (17 percent). Except for use of the shunt, the surgical technique was identical in the two groups of patients.

The effect of "ischemic" blood on transmembrane potentials of normal porcine ventricular myocardium.

"Ischemic" blood was obtained in pigs from a local coronary vein on release of coronary artery occlusion. The effects of this blood on transmembrane potentials of muscle strips taken from the same heart were compared with control blood. Whereas action potentials remained stable in control blood, ischemic blood collected after more than 15 minutes of coronary occlusion produced shortening of action potential duration, reduction of resting potential, upstroke velocity and amplitude, then postrepolarization refractoriness and finally unresponsiveness. Ischemic blood collected after shorter periods of coronary occlusion produced only mild effects (shortening of action potential and postrepolarization refractoriness). These effects of ischemic blood could not be attributed to increased potassium concentration even in combination with acidosis, hypoxia and hypoglycemia. It appears that during ischemia unidentified factors are released which have potent depressant effects on the excitability of even normal myocardium.

Persistence of myocardial injury following brief periods of coronary occlusion.

Transient (20 min) occlusion of the left anterior descending coronary artery in open-chest anaesthetized dogs caused immediate aneurysmal bulging of the ischaemic segment, which preceded epicardial ST-segment elevation. Reperfusion after 20 min restored epicardial electrograms to normal, wheras mechanical dysfunction persisted for a least 45 min therafter. The study shows that there is temporal disparity between electrical and mechanical events both at the inception of myocardial ischaemia and during recovery from transient myocardial ischaemia.

On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs

Propranolol has been shown to reduce the extent of necrosis that develops after temporary coronary occlusion in dogs. To determine whether this protective action was related to beta adrenergic blockade or to direct effects, necrosis was quantitated in the posterior papillary muscle 2 to 4 days after 40 minute periods of coronary occlusion in anesthetized open chest dogs. Groups of dogs either were untreated or were pretreated with doses of d,l-propranolol, 0.005 to 5 mg/kg body weight, or doses of d-propranolol 2.5 or 5 mg/kg. Necrosis was greatly reduced in dogs treated with 5 mg/kg of d,l-propranolol. This protective effect was significant but quantitatively less with 0.5 and 0.05 mg/kg of d,l-propranolol. A dose of 0.005 mg/kg d,l-propranolol and d-propranolol failed to alter myocardial necrosis significantly. The dose-related reduction of necrosis with d,l-propranolol correlated with a similar dose relation for beta adrenergic blockade and suggested that a protective effect was related to beta blockade. The reduction of necrosis with 0.05 and 0.5 mg/kg of d,l-propranolol (a level at which direct “membrane stabilizing” effects are insignificant) suggested that direct effects were not essential for protection. The negative results with d-propranolol further support our conclusion that propranolol reduces myocardial ischemic injury through beta adrenergic blockade rather than through direct myocardial actions.

Coronary hemodynamics during reperfusion following acute coronary ligation in dogs

The coronary hemodynamic effects of re-establishing blood flow to ischemic myocardium and the regional distribution of myocardial flow during reperfusion were studied in anesthetized open-chest dogs. A large portion of the left ventricular wall was rendered ischemic by occlusion of the left anterior descending coronary artery for 2 hours. During reperfusion of the LAD, coronary resistance in the reperfused vasculature increased progressively for the first 3 hours, while resistance in the intact LC vasculature was unchanged. Minimal resistances in the reperfused vascular bed, calculated from mean aortic pressure and peak coronary reactive hyperemic blood flow following a 90 sec. LAD occlusion, were elevated significantly during reperfusion. The increased minimal resistance values, which reflect the passive physical component of resistance, indicate structural changes in the reperfused vascular bed which were evident shortly after the initiation of reperfusion and persisted throughout the experimental period. Coronary resistances (R H) in the reperfused (LAD) and intact (LC) vasculatures during the reactive hyperemia following 10 sec. coronary occlusions were evaluated. During reperfusion, R H in the reperfused vasculature increased progressively while R H in the intact bed was unchanged. The marked increase in R H in the LAD indicates that the reactive hyperemic flow response to a consistent period of coronary occlusion progressively diminished, and reflects a gradual reduction in the vasodilatory potential of the reperfused coronary circulation. The regional distribution of myocardial blood flow following 5 minutes, 2 hours, and 4 hours of reperfusion was measured with multiple injections of radioactive microspheres. These measurements demonstrated a progressive reduction of blood flow to the reperfused myocardium with no significant change in flow to the control myocardium. In contrast to the uniform transmural distribution of flow in the normal myocardium, the reperfused region showed a distinctly nonuniform distribution of flow after 2 hours and 4 hours of reperfusion, with more severe reduction of flow to the endocardial layer. These studies would suggest that rechannelling blood flow distal to an acute coronary occlusion in human subjects might not in itself be capable of reversing the myocardial injury. It is hoped that additional therapeutic measures might be applied to salvage the injured myocardium.

Contractile and biochemical effects of coronary reperfusion after extended periods of coronary occlusion

The effects of coronary reperfusion on recovery of regional myocardial contractility and high energy phosphate levels were studied In dogs after various periods of coronary occlusion. Segmental changes in myocardial contractility were measured by means of a strain gaugetipped, two-pronged catheter probe that measures myocardial fiber shortening. The curves of contraction are sensitive to the effects of ischemia. Coronary occlusion resulted in a rapid replacement of fiber shortening by passive fiber lengthening. If coronary occlusion was released and blood flow restored within 45 minutes, myocardial contractility returned promptly; adenosine triphosphate and creatine phosphate values were restored to normal. With coronary occlusion of 1 hour or longer, contractility failed to return in the immediate postperfusion period, but delayed return was recorded after 2 weeks of reperfusion. The extent of such recovery varied with the duration of preceding occlusion. Thus, reperfusion after 1 hour of occlusion was followed by return of fiber shortening over the entire reperfused region. With 2 hours of occlusion, recovery occurred over 75 percent of the reperfused myocardium. With 3 hours of occlusion followed by reperfusion, recovery of contractility was only partial, comprising approximately 60 percent of the reperfused region. High energy phosphate content of the reperfused myocardium showed a similar pattern of recovery. With occlusion of longer duration, reperfusion failed to restore contractility to any significant extent. These findings indicate that reperfusion after coronary occlusion of 1 to 3 hours may restore contractility over a period of 2 weeks, but the extent of such recovery diminishes with the increase in the duration of occlusion.

Regulation of postocclusive hyperemia by endogenously synthesized prostaglandins in the dog heart.

Experiments were performed to evaluate the role of prostaglandin synthesis in the regulation of coronary blood flow in dog hearts. The left main coronary artery was cannulated and flow measured both in otherwise intact animals and in canine heart-lung preparations. Prostaglandin E was measured by radioimmunoassay. Reactive hyperemia (flow after occlusion release) was induced by coronary occlusion for 10, 15, and 20 s and was 39 plus or minus 13 (mean plus or minus SEM), 66 plus or minus 21, and 82 plus or minus 24 ml, respectively. Indomethacin, an inhibitor of prostaglandin synthetase, reduced reactive hyperemia at 10, 15, and 20 s to 15 plus or minus 5, 33 plus or minus 11, and 47 plus or minus 17 ml, respectively (P smaller than 0.05). Meclofenamate, a different prostaglandin synthetase inhibitor, gave similar results. In a second group of five dogs, prostaglandin production of the heart was examined in response to 20-s occlusions. There was a significant increase in prostaglandin production from a basal level of 18.6 plus or minus 4.9 mg/min to 35.3 plus or minus 5.8 ng/min after occlusion of the coronary artery for 20 s (P smaller than 0.05). After indomethacin, this increase in prostaglandin production was not observed and reactive hyperemia was significantly reduced. Thus, prostaglandin synthesis appears to be important to modulating canine coronary blood flow in response to brief periods of coronary occlusion.

Persistence of myocardial injury following brief periods of coronary occlusion

Persistence of myocardial injury following brief periods of coronary occlusion

Effect of Aminophylline on Myocardial Reactive Hyperemia

SummaryThe effect of aminophylline on the coronary vasodilator effect of adenosine and myocardial reactive hyperemia following different periods of coronary occlusion was studied in 5 anesthetized dogs. It has been shown that aminophylline decreases the volume and duration of hyperemic flow produced by adenosine approximately 41 and 11%, respectively, and by ischemia, approximately 42 and 31%, respectively. These results support the concept that adenosine is possibly a metabolic mediator in the regulation of coronary blood flow.

MYOCARDIAL REACTIVE HYPEREMIA IN THE UNANESTHETIZED DOG.

Studies of myocardial reactive hyperemia in dogs 5–24 days after the implantation of electromagnetic flowmeters on coronary artery branches reveal that the duration of occlusion and the control flow rate are independent determinants of the volume of reactive hyperemia flow. Flow debt is almost always overpaid, the average figure being 500 ± 200%. Phasic coronary flow curves show an increase in both systolic and diastolic flow during reactive hyperemia, the increase in systolic flow being due in part to decreased myocardial contractility. Myocardial reactive hyperemia is thought to be due to the accumulation of vasodilator metabolites during the period of coronary occlusion.