Bharat Patel

Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile

Myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a means to assess myocardial infarct size during coronary occlusion and to quantify the extent of salvaged myocardium after coronary occlusion followed by reperfusion. Open chest dogs underwent either a permanent coronary artery occlusion (Group 1, n = 16) or a 2 h occlusion followed by reperfusion (Group 2, n = 15). Animals in both groups were killed 48 h after occlusion. During coronary occlusion, 23 of the 25 dogs that survived the coronary occlusions had abnormal myocardial scintigrams. The scintigraphic perfusion defect size correlated well with the pathologic infarct size (r = 0.85 and 0.95 by planar and tomographic imaging, respectively). The planar scintigraphic defect size, but not the tomographic defect size, overestimated the pathologic size. The planar scintigraphic defect size observed during coronary occlusion was markedly reduced 48 h after reperfusion (24.8 +/- 12.8% to 10.6 +/- 9.7% of the left ventricle, p less than 0.003). The uptake of technetium-99m hexakis 2-methoxyisobutyl isonitrile in the ischemic myocardium increased significantly 48 h after reperfusion (p less than 0.003) and correlated with the increase in regional myocardial blood flow, as assessed by radioactive microspheres (r = 0.83, p less than 0.01). Thus, myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile allows reliable demonstration of the presence of acute infarction, estimation of infarct size and quantification of the extent of salvaged myocardium after coronary reperfusion.

An angiographic and histologic study of cocaine-induced chest pain

Abstract Chest pain is not an uncommon symptom in patients who abuse cocaine. A small number also develop acute myocardial infarction. 1,2 Most, however, show electrocardiographic ST-segment or T-wave abnormalities as the only objective evidence of myocardial ischemia. Coronary artery spasm has been popularly invoked as the possible cause for chest pain. 3,4 However, evidence for spasm is largely circumstantial at present. An alternative source of pain may be myocarditis, 5 which has been demonstrated in some patients dying of cocaine abuse. 6,7

An accurate, nontraumatic ultrasonic method to monitor myocardial wall thickening in patients undergoing cardiac surgery☆

Measurement of systolic wall thickening by sonomicrometry provides an accurate index of regional left ventricular function, but the trauma of crystal insertion limits its widespread clinical use. The first clinical application of a 10 MHz ultrasonic Doppler probe that can be either sutured or applied by suction to the epicardium and can measure wall thickening at any depth of the left ventricular wall is described. In 18 dogs, measurements obtained with the suction probe correlated well (r = 0.97) with those of a previously validated sutured probe. To assess clinical feasibility, the probe was applied to the epicardium of patients undergoing coronary bypass surgery. Good quality wall thickening signals were obtained with no complications. Transmural left ventricular thickening fraction before bypass surgery was 34 +/- 3% (mean value +/- SE) at the mid-ventricular lateral wall, 33 +/- 4% at the anterior basal wall and 26 +/- 4% at the mid-ventricular posterior wall. Right ventricular thickening fraction averaged 25 +/- 3%. Endocardial thickening fraction tended to exceed epicardial thickening fraction, although the difference attained statistical significance (p less than 0.05) only at the anterior basal wall. On average, thickening fraction during the immediate postoperative period remained unchanged compared with the preoperative values, but a marked individual variability was observed, with 7 of 15 patients exhibiting a decrease and 8 an increase. Exteriorization of the wires attached to the sutured probe allowed continuous in situ monitoring of wall thickening in the postoperative period and subsequent removal of the probe. In six patients the crystal was left in place for 48 to 72 h after surgery and then removed without complications; good wall thickening signals were obtained for the entire period during which the probe was implanted. Thus, the Doppler probe is an accurate, atraumatic method for measuring right and left ventricular regional function. Transmural, endocardial and epicardial function can be mapped at various sites during surgery, and post-operatively one can monitor serial changes of regional function and assess the effects of cardioplegia and other therapeutic interventions. This technique should be useful for both investigative and clinical purposes.

Factors that determine the occurrence of reperfusion arrhythmias

The determinants of reperfusion arrhythmias were investigated in 63 open-chest dogs undergoing a 25-minute coronary artery occlusion followed by reperfusion. Heart rate correlated positively with the occurrence of reperfusion ventricular tachycardia (VT) and ventricular fibrillation (VF). Collateral flow during ischemia (radioactive microspheres) exhibited a strong negative correlation with the incidence of both VT and VF upon reperfusion. Importantly, a sensitive coupling was present, whereby small differences in flow were associated with large differences in rhythm disorders. The rise in intramyocardial CO2 tension (another index of severity of ischemia) was greater in dogs exhibiting reperfusion VT (p less than 0.001) and VF (p less than 0.08); however, this variable was significantly correlated with collateral flow (r = -0.57, p less than 0.01). The size of the occluded coronary bed, determined by postmortem perfusion, was not consistently related to VT; within a given range of occluded bed sizes, the incidence of VT was inversely related to collateral flow. Thus, reperfusion-induced VT is relatively independent of the size of the occluded bed, and is determined primarily by the degree of myocardial hypoperfusion. In contrast, VF did not develop with occluded beds less than 25% of the left ventricular mass; above this critical occluded bed size, its incidence was inversely related to collateral perfusion. Reperfusion VF is therefore determined by the association of a large occluded bed with a poor collateral flow. This study identifies and systematically analyzes three major determinants of reperfusion arrhythmias: (1) the severity of antecedent ischemia, estimated either from the degree of flow reduction or the rise in intramural CO2 tension; (2) the amount of ischemic/reperfused myocardium; and (3) the heart rate. In addition to conceptual interest and clinical implications, the findings have important implications for the design of future studies aimed at evaluating antiarrhythmic interventions in experimental models.

Evidence for Free Radical Generation in Vivo during Cardiac Ischemia and Reperfusion

Myocardial stunning results from reperfusion of a zone of heart muscle that has been subjected to ischemia for a period of less than 20 min (10). Although stunning usually results in temporary disruption of heart function, it does not appear to result in death of myocytes which is characteristic of longer periods of ischemia followed by reperfusion (21). Recovery of viable tissue in the reperfused zone after more extensive periods of ischemia is a function of the time of coronary occlusion. Based on the observation of a number of investigators, it became apparent that reoxygenation of anoxic tissues was detrimental to those tissues, but not as detrimental as would be the case if there were no reoxygenation at all. The oxygen paradox concept was set forth by Hearse and colleagues (8) who determined that there were ultra-structural changes in myocytes which occurred as a result of reoxygenation of ischemic heart tissue (9). Other investigations suggested that oxygen free radicals might be involved in reperfusion injury to tissues in general due to the conversion of xanthine dehydrogenase to xanthine oxidase during ischemia (7). In addition, other possible sources of radical production have been implicated, including activated neutrophils (22,23) and cellular redox functions such as the mitochondrial transport system (17) and eicosanoid metabolism (5,24). Factors which inhibit or modulate the in vitro activities of these various sources of radical production and which have been reported to provide some protection against reperfusion tissue injury when administered in vivo constitute the basis for the implications (prostaglandin synthesis inhibitors, superoxide dismutase (15), oxypurinol (19), free radical scavengers (16), iron chelators (3), etc.).

Ultrasonic Sensors For Measuring Regional Ventricular Function

Measurement of systolic wall thickening by sonomicrometry is an accurate index of regional left ventricular (LV) function, but the trauma of crystal inserion precludes its clinical use. We have developed a 4-mm 10 MHz ultrasonic probe which can either be sutured or applied via suction to the epicar-diuui and can measure wall thickening at anv depth of the LV wall. In 18 dogs, the suction probe correlated well (r=0.97) with previously validated sutured probe. To assess clinical feasibility, the probe was applied to the epicardium of 45 patients undergoing coronary bypass surgery. Good wall thickening tracings were obtained with no trauma. Transmural LV thickening fraction prior to bypass surgery was 32 ± 6 % (X ± SEM) at the midventricular lateral wall, 29 ± 5 % at the anterior basal wall and 25 ± 5 % at the midventricular posterior wall. Right ventricular thickening fraction averaged 25 ± 4 %. In general, wall thickening during immediate postoperative period remained unchanged compared to preoperative thickening fraction. Exteriorization of a wire attached to the sutured probe allows in situ monitoring of wall thickening for 48-72 h after surgery and subsequent removal. Thus, this probe is an accurate, atraumatic method for measuring right and LV regional function. Transmural, endocardial and epicardial function can be mapped at various sites during surgery and post-operatively one can follow serial changes of regional function and assess the effects of cardioplegia and other therapeutic interventions.