Colin M. Bloor

Evaluation of a QRS scoring system for estimating myocardial infarct size

This study correlated the location and size of posterolateral myocardial infarcts (MIs) measured anatomically with that estimated by quantitative criteria derived from the standard 12-lead ECG. Twenty patients were studied who had autopsy-proved, single, posterolateral MIs and no confounding factors of ventricular hypertrophy or bundle branch block in their ECG. Left ventricular anatomic MI size ranged from 1 to 46%. No patient had a greater than or equal to 0.04-second Q wave in any electrocardiographic lead and only 55% had a 0.03-second Q wave. A 29-point, simplified QRS scoring system consisting of 37 weighted criteria was applied to the ECG. Points were scored by the ECG in 85% of the patients (range 1 to 8 points). MI was indicated by a wide variety of QRS criteria; 19 of the 37 criteria from 8 different electrocardiographic leads were met. The correlation coefficient between MI size measured anatomically and that estimated by the QRS score was 0.72. Each point represented approximately 4% MI of the left ventricular wall.

Adaptations of the left ventricle to chronic pressure overload.

Left ventricular (LV) function during the adaptation to chronic pressure overload produced by an ascending aortic constriction was analyzed in conscious dogs, instrumented with intraventricular micromanometers and pairs of ultrasonic crystals for measurement of LV wall thickness (WTh) and internal LV chamber diameter. During inflation of the cuff to produce LV pressures averaging 220 mg Hg, calculated peak wall stress (WSt) increased by 55% above control while percent shortening decreased by 24% and mean circumferential shortening velocity (VCF) decreased by 39% from control. By 9 days (mean) after aortic constriction, the cross-sectional area (CSA) of the LV wall increased by 10% and peak WSt fell to 37% above control. End-diastolic diameter (EDD) increased to 4% above control, while percent shortening and mean VCF remained reduced at -12% and -20% of control, respectively. During the phase of concentric hypertrophy (mean 2 1/2 weeks), CSA increased further to 15% above control and WSt fell to 22% above control, while EDD and percent shortening returned to control and mean VCF increased to -7% of control (not significant). At 24 hours after release of the cuff WSt, percent shortening, mean VCF, and peak velocity of LV pressure rise (peak dP/dt) were not significantly different from control. Rapid, partial regression of hypertrophy was observed in some dogs. Thus, the left ventricle responds to chronically elevated pressure by initial dilation with increased WSt followed by gradual wall thickening and consequent reduction of WSt to near normal. After successful adaptation to the pressure overload, hypertrophy per se did not produce intrinsic depression of the myocardial inotropic state.

Coronary Artery Reperfusion: I. EARLY EFFECTS ON LOCAL MYOCARDIAL FUNCTION AND THE EXTENT OF MYOCARDIAL NECROSIS

The effects of coronary artery reperfusion 3 hr after coronary occlusion on contractile function and the development of myocardial damage at 24 hr was studied experimentally. In 14 control and 6 reperfused dogs, relationships between epicardial ST segment elevation 15 min after coronary occlusion and myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 hr later were examined. The electrocardiograms were recorded from 10 to 15 sites on the left ventricular epicardium and transmural samples for CPK and histology were obtained from the same sites where epicardial electrocardiograms had been recorded. An inverse relation existed between ST segment elevation (mv) 15 min after occlusion and log CPK activity (IU/ mg of protein) 24 hr later, log CPK = - 0.06ST + 1.26. In dogs subjected to coronary artery reperfusion, there was significantly less CPK depression (log CPK = - 0.01ST + 1.31, [P < 0.01]) than that expected from the control group. In the control group 97% of specimens showing ST segment elevations over 2 mv at 15 min showed abnormal histology 24 hr later. In contrast, in the reperfused group 43% of sites exhibiting elevated ST segment at 15 min showed abnormal histology 24 hr later. In six additional dogs it was shown that the paradoxical movement of the left ventricular wall could be reversed within 1 hr of perfusion. Therefore, by enzymatic and histologic criteria, as well as by functional assessment, coronary artery reperfusion 3 hr after occlusion resulted in salvage of myocardial tissue.

Evaluation of a QRS scoring system for estimating myocardial infarct size. II. Correlation with quantitative anatomic findings for anterior infarcts

The ability of an independently developed QRS point score to estimate the size of infarcts predominantly within the anterior third of the left ventricular was evaluated by quantitative pathologic-electrocardiographic correlation. The study was limited to 21 patients with a single infarct documented by postmortem examination, for whom an appropriately timed standard 12 lead electrocardiogram was available that did not exhibit signs of left or right ventricular hypertrophy, left or right bundle branch block or anterior or posterior fascicular block. At necropsy the heart was cut into five to seven slices. The location and size of the infarct was quantitated by computer-assisted planimetry of the slices. The electrocardiogram of 19 (90 percent) of the patients exhibited either a Q wave or an R wave of no more than 20 ms in lead V2. The infarct in the two patients without this electrocardiographic finding was small, occupying 2 and 3 percent of the left ventricle, respectively. The percent infarction of the left ventricle correlated with the QRS point score (r=0.80). Thus in patients without complicating factors in the electrocardiogram and with a single infarct, the electrocardiogram provides a marker for infarction in the anterior third of the left ventricle and permits estimation of infarct size.

Regional myocardial function and dimensions early and late after myocardial infarction in the unanesthetized dog.

SUMMARY Pairs of ultrasonic dimension gauges and a micromanometer implanted in the subendocardium of the left ventricles of unanesthetized dogs were used to analyze serial changes in hemodynamic status and segmental function for up to 4 weeks after permanent circumflex coronary artery occlusion. Regional function was studied in control segments and in segments identified as marginal (hypokinetic) and ischemic. In three dogs, after transient regional dysfunction, no myocardial infarction developed, whereas in five dogs regional dysfunction at 3 hours after occlusion was followed by the development of persistent dysfunction and infarction. Left ventricular end-diastolic segment length (EDL) changes over time; EDL of the control segments increased progressively, but in marginal segments EDL was 12% below control and in the ischemic segments 30% below control by 4 weeks. Progressive increases in percent active shortening occurred in control segments, but holosystolic bulging was replaced by akinesia in ischemic segments, and persistent reduction in shortening was present in marginal segments at 4 weeks. Correlations were found between percent scar and reductions in percent shortening, EDL, and the ratio of change in diastolic length to change in diastolic pressure. These methods have detected hyperfunction in normal regions and variable segmental loss of contractile function, together with reduction of subendocardial dimensions and changes that may reflect decreased diastolic compliance in ischemic regions. We conclude that this model for the conscious animals may be useful for studying the influence of therapy on the extent of myocardial damage after experimental coronary occlusion.

Effect of Glucose-Insulin-Potassium Infusion on Myocardial Infarction following Experimental Coronary Artery Occlusion

The effects of glucose-insulin-potassium (GIK) infusion and glucose (G) infusion started 30 min after experimental coronary occlusion and the combination of GIK and propranolol (P) started 3 hours after coronary occlusion on the development of myocardial infarction were studied in 37 dogs. Fifteen minutes after the coronary occlusion, epicardial electrocardiograms were recorded at 10-15 sites; 24 hours later transmural specimens were obtained from the same sites for determination of myocardial creatine phosphokinase (CPK) activity and the evaluation of morphologic changes. In the control group (normal saline infusion) the relationship between S-T-segment elevation (mv) 15 min after occlusion and CPK activity (IU/mg of protein) 24 hours later was: log CPK = −0.064 S-T + 1.24; r = 0.81. In the GIK group, the infusion was begun 15 min following epicardial mapping, and sites with the same S-T-segment elevations showed less CPK depression than did the control group: log CPK = −0.022 S-T + 1.25. The G group also showed less CPK depletion than the control group but to a somewhat lesser extent than the GIK group (log CPK = −0.030 S-T + 1.20). The group receiving GIK and P 3 hours after occlusion also showed less CPK depression than did the control group (log CPK = −0.034 S-T + 1.26). Histologic analysis in 24-hour specimens showed that sites which exhibited S-T-segment elevation 15 min after occlusion showed normal histology in 3% of specimens obtained from control dogs, while the other 97% showed early signs of myocardial infarction. However, in the GIK group, 36% of the specimens with S-T-segment elevation prior to the infusion were histologically normal 24 hours later, while in the G group 30% were normal, and in the GIK and P group 17% were normal. Electron microscopy confirmed the morphologic changes observed by light microscopy. Thus, in the presence of experimental coronary occlusion, GIK exerts a protective effect against myocardial ischemia and reduces the extent of myocardial necrosis. G alone acts similarly but to a lesser degree, while a beneficial effect can also be demonstrated when GIK and P are started 3 hours after the onset of coronary occlusion.

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (ST) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronary occlusion. In the control group ST and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, ST fell from 3.5+/-0.8 to 1.1+/-0.4 mV (P<0.01) and NST was reduced from 6.7+/-1.1 to 1.4+/-0.8 (P<0.01). In order to study the influence of hydrocortisone on necrosis, epicardial ST segment elevation 15 min after coronary occlusion was compared to myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 h later in each site. In a control group (14 dogs) a relationship was established between ST segment elevation at 15 min (in millivolts) and CPK activity (in international units per milligram of protein) 24 h later: log CPK = -0.0611ST + 1.26 (N = 102 specimens, r = -0.79). In the treated groups, hydrocortisone (50 mg/kg i.v.) was given either at 30 min after occlusion (seven dogs) or at 6 h after occlusion (six dogs). Both groups received supplementary doses of hydrocortisone (25 mg/kg) 12 h after occlusion. The two treated groups exhibited less CPK depression than that expected from ST segment elevation at each site, with slopes of the regression lines which were significantly less steep: log CPK = -0.0288ST + 1.26 (N = 48, r = -0.71) and log CPK = -0.0321ST + 1.31 (N = 48, r = -0.76) in the (1/2) h and 6 h groups, respectively. Histologically, sites with ST segment elevations of less than 2 mV at 15 min after occlusion exhibited normal appearance 24 h later. Sites with ST segment elevations (> 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion.

Coronary collateral development in swine after coronary artery occlusion.

We have quantified the development of the coronary collateral circulation in the pig. The collateral circulation was induced to grow by placing an ameroid occluder on the left circumflex coronary artery. Two to 16 weeks after ameroid placement, the coronary collateral circulation was identified after the injection of several colors of a silicone polymer into the coronary arteries and the aorta. We identified intercoronary and extracardiac collaterals and quantified their number, location, size, and wall thickness. Intercoronary collaterals grew to a level that represents a 14-fold increase in normal collateral blood flow under resting conditions compared with the values in an animal not subjected to coronary artery occlusion. Extracardiac collaterals could potentially supply approximately 30% of resting flow. The sources of the extracardiac collaterals were the bronchial and internal mammary arteries. Coronary collateral morphometry and DNA synthesis in the pig heart also were examined. Coronary collaterals had significantly less smooth muscle than did normal arterioles. This may account, in part, for the reduced response of the coronary collaterals to vasodilators. We observed intense DNA synthesis in endothelial and smooth muscle cells in the first 2 or 3 weeks of ischemia. However, DNA synthesis rapidly ceased after this time, coincident with coronary collateral reserve values (ischemic/nonischemic regional blood flow ratios during maximal vasodilation) reaching their maximum level. This suggests that failure of the vessels to continue proliferating accounts for the occurrence of the plateau in blood flow levels.

Regional myocardial blood flow during acute myocardial infarction in the conscious dog.

Regional myocardial blood flow was studied in the conscious dog at periods of 5 minutes to 4 days after occlusion of a major branch of the left coronary artery. Dogs were instrumented with aortic electromagnetic flow probes, occlusive cuffs on either the anterior descending or circumflex branch of the left coronary artery, and a left atrial Silastic catheter for injection of microspheres (IS ± 5 &mgr;m) labeled with either 55Sr, 141Ce, or 51Cr. Microspheres were injected into 25 fully conscious dogs during three of the following time periods: control preocclusion and 0.1, 2, 6, 24, or 96 hours postocclusion. In the conscious dog, before occlusion, the endo-cardial half of the left ventricular myocardium received 28% more blood flow than the epicardial half. After sudden occlusion of a coronary artery branch, there was a marked reduction in blood flow as well as an alteration in distribution of blood flow within the ischemic tissue; blood flow was most severely reduced in the subendocardial center of the ischemic region, less so in the epicardial ischemic region, and least reduced in the marginal region of the infarct. Blood flow was increased to the nonischemic tissue. There was no change in this pattern of reduced blood flow by 6 hours postocclusion, but by 24 hours, flow was moderately increased to all areas except the central subendocardial core, and was further increased at 96 hours. Blood flow to the endocardial half of the left ventricular myocardium averaged 63 ml/100 g per min during the control period, was reduced to 12–18 ml/100 g per min at 0.1–6 hours in the ischemic region, increased to 29 ml/100 g per min at 24 hours, and to 48 ml/100 g per min by 96 hours. These findings indicate that there is a reversal of the flow ratio within ischemic myocardium with relative under-perfusion of the endocardial half of the wall, which is not corrected by 4 days. There is a modest increase of collateral blood flow to ischemic tissue by 24 hours and this increase is considerably augmented by % hours, apparently as a result of the growth and enlargement of collateral vessels.

Reduction by Hyaluronidase of Myocardial Necrosis following Coronary Artery Occlusion

Electrocardiographic, enzymatic, and morphologic signs of myocardial ischemic injury following coronary occlusion have previously been shown to be ameliorated by reducing myocardial oxygen requirements, and/or by increasing the availability of oxygen as well as of substrates for anaerobic ATP production. Since hyaluronidase increases diffusion through the extracellular space and may facilitate delivery of substrates to ischemic cells, the influence of its administration on the size of experimentally produced infarcts was studied. In 14 control dogs epicardial electrocardiograms were taken in 10-15 sites on the anterior surface of the left ventricle before and after occlusion of the left anterior descending coronary artery. Twenty-four hours later, transmural specimens were obtained from the same sites from which electrocardiograms had been recorded, and were analyzed for creatine phophokinase (CPK) activity, for histologic changes, and glycogen content. In control dogs, sites exhibiting S-T-segment elevation 15 min after occlusion showed early structural signs of necrosis and glycogen depletion in 97% of specimens taken after 24 hours. The relationship between S-T-segment elevation at 15 min (mv) and CPK activity 24 hours later (IU/mg protein) was log CPK = −0.061 S-T + 1.26. Hyaluronidase (225 u/kg) was given to 15 dogs; no hemodynamic changes occurred but the depression of CPK activity was reduced following occlusion; log CPK = −0.024 S-T + 1.28. Similarly, only 55% of sites that showed S-T-segment elevation prior to hyaluronidase administration exhibited histologic signs of early infarcts and glycogen depletion 24 hours later. It is concluded that hyaluronidase diminished myocardial necrosis following acute coronary occlusion.