Samon Koyanagi

Abnormalities in the coronary circulation that occur as a consequence of cardiac hypertrophy

Myocardial ischemia is frequently observed in patients with cardiac hypertrophy even when the conduit coronary arteries are normal. Recent studies indicate that impaired coronary reserve in hypertrophied hearts probably occurs because growth of the coronary bed does not keep pace with increases in cardiac mass. The imbalance between vascular proliferation and muscle growth is probably most severe when cardiac hypertrophy is produced by pressure overload. Experimental studies also suggest that abnormalities intrinsic to pressure-hypertrophied heart muscle (decreased capillary density; decreased coronary reserve; electrophysiologic abnormalities) adversely affect the response of the enlarged heart to sudden coronary occlusion. When animals with hypertension and left ventricular hypertrophy are subjected to sudden coronary occlusion, the incidence of sudden cardiac death is increased severalfold and infarct size is substantially augmented. These observations suggest that abnormalities in the coronary microcirculation that accompany cardiac hypertrophy play a significant role in the pathogenesis of the complications associated with cardiac hypertrophy.

Detection of acute myocardial infarction in closed-chest dogs by analysis of regional two-dimensional echocardiographic gray-level distributions.

We hypothesized that acute myocardial infarction could be detected in standard two-dimensional echocardiograms of closed-chest dogs by evaluating regional echo amplitude distribu-tions using computerized image analysis. We tested this hypothesis by performing standard, 2.4 MHz two-dimensional echoes before and 2 days after circumflex coronary occlusion in seven closed-chest dogs. Control and infarcted regions of interest were studied in digitized stop-frame images. Average gray level was calculated for each region of interest, and the shape of the gray-level distribution was analyzed by calculation of skewness and kurtosis and by qualitative features of shape. Average gray level increased significantly from the pre-to postocclusion images in the infarcted regions (16.7 ± 4.2 vs. 32.4 ± 4.4 units, P < 0.01), but not in the control regions (17.4 ± 4 vs. 22.3 ± 5.5., P = NS). Average gray level could not distinguish between infarcted and normal regions within the postocclusion images (36 ± 5.2 vs. 33.6 ± 5.8, P = NS). Three independent observers qualitatively evaluated histogram shape and correctly identified 7/7 MI regions (100% sensitivity) and 14/20 normal regions (70% specificity). Quantitatively, infarct regions exhibited a significant decrease in kurtosis (2.8 ± 0.9 to 0.44 ± 0.5, P < 0.01); the normal regions showed no significant change in kurtosis from pre-to postocclusion images (7.1 ± 4.0 vs. 5.2 ± 2.9, P = NS). Within postocclusion images, infarcted regions displayed a significantly lower kurtosis than did normal regions (0.27 ± .47 vs. 2.5 ± 1.0, P < .01).

Effects of chronic hypertension and left ventricular hypertrophy on the incidence of sudden cardiac death after coronary artery occlusion in conscious dogs

When acute myocardial infarction occurs in patients with hypertension and left ventricular hypertrophy (LVH), the incidence of sudden cardiac death increases markedly. Possible explanations include increased size of the occluded vascular bed secondary to more extensive atherosclerotic coronary vascular disease in the presence of hypertension, decreased coronary reserve secondary to LVH, and intrinsic electrophysiologic abnormalities in hypertrophied cardiac muscle. To explore these possibilities, we produced acute circumflex coronary occlusion during the resting, conscious state in 32 control dogs and in 28 dogs with hypertensive LVH. Before coronary occlusion, mean arterial pressure was 96 ± 0.1 mm Hg in control dogs and 125 ± 5 mm Hg in dogs with hypertensive LVH (p < 0.01). The control left ventricular/body weight ratio was 4.5 ± 0.1 g/kg, compared with 6.1 ± 0.1 g/kg in hypertensive LVH (p < 0.01). Cumulative mortality at 6, 24 and 48 hours was 9%, 13% and 16% in control dogs and 32%, 43% and 54%, respectively, in dogs with hypertensive LVH (all p < 0.01 vs control). The perfusion fields of the occluded vessel defined by postmortem coronary angiography were similar in the two groups (31 ± 2% of left ventricular mass for control vs 29 ± 2% for hypertensive LVH). Thus, the increased incidence of sudden cardiac death after coronary artery occlusion in hypertensive LVH dogs cannot be explained by increased size of the occluded vascular bed and is probably related to the decreased coronary reserve or intrinsic electrophysiologic abnormalities that characterize pressure-induced hypertrophied cardiac muscle.

Relations between 2-dimensional echocardiographic wall thickening abnormalities, myocardial infarct size and coronary risk area in normal and hypertrophied myocardium in dogs

Systolic wall thickening abnormalities are sensitive indicators of ischemia and infarction. One purpose of this investigation was to assess the relation between coronary risk area, infarct size and wall thickening abnormalities (dyskinesia) using 2-dimensional echocardiography (2-D echo) in a closed-chest conscious dog model of acute myocardial infarction. The second purpose was to study the effects of systemic hypertension (SH) and left ventricular (LV) hypertrophy on these relations. Our hypothesis was that the infarct size and the extent of 2D echocardiographic dyskinesia would be quantitatively different in SH-LV hypertrophy, a condition in which coronary vascular reserve is diminished. Permanent circumflex coronary occlusion was performed in 15 conscious normal dogs and in 14 dogs with LV hypertrophy secondary to renal hypertension. Two-dimensional echocardiograms were obtained before, 20 minutes after and 2 days after coronary occlusion. The systolic wall thickening along 12 equidistant radii was analyzed in short-axis images. Percent dyskinesia on 2-D echo was defined as the percentage of radii showing systolic thinning. Infarct size was determined pathologically and risk area was determined angiographically. For a given risk area, coronary occlusion resulted in a larger infarction in dogs with SH-LV hypertrophy than in normal dogs (p less than 0.05). Two-dimensional echocardiographic dyskinesia correlated well with infarct size both at 20 minutes (r = 0.92) and 2 days (r = 0.94); dyskinesia modestly overestimated the infarct size and underestimated the risk area. The relations were similar in both normal and SH-LV hypertrophy groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial infarct size threshold for two-dimensional echocardiographic detection: Sensitivity of systolic wall thickening and endocardial motion abnormalities in small versus large infarcts☆

This study evaluated the ability of 2-dimensional echocardiography to detect myocardial infarcts of varying sizes. Echocardiography was performed in 29 closed-chest, conscious dogs 2 days after circumflex coronary artery occlusion, and the ultrasonic recordings were analyzed for regional abnormalities in either wall thickening or endocardial motion. Acute myocardial infarct (AMI) size and extent were assessed by morphologic examination. In 5 dogs, coronary occlusion failed to produce AMI; in these dogs wall thickening analysis showed no abnormalities (100% specificity), and endocardial motion analysis yielded 1 false-positive result (80% specificity). In 24 dogs an AMI developed; infarcts larger than 18% of left ventricular mass uniformly resulted in echocardiographically detectable contraction abnormalities. When the AMI was small (1 to 6% of left ventricular mass) and primarily subendocardial, the sensitivity of echocardiography was poor: Only 3 of 10 of the dogs with a small AMI had abnormalities by wall thickening, and only 1 of 10 by endocardial motion. Thus, in this canine model of AMI, 2-dimensional echocardiography was insensitive to small, subendocardial AMI. If this is so in humans as well, it is a potential limitation of the clinical use of echocardiography in the detection of AMI.

Role of afterload in determining regional right ventricular performance during coronary underperfusion in dogs.

The relationship between coronary perfusion pressure and regional myocardial performance of the right ventricular free wall was studied, in the presence or absence of right ventricular hypertension in 13 open-chest dogs. The right coronary artery was perfused through a shunt from a carotid artery. Regional systolic shortening of the right ventricular free wall was measured by means of a sonomicrometric technique at various levels of coronary perfusion pressure. Regional shortening was insensitive to coronary perfusion pressure or flow when it was above 31 mm Hg or 0.27 ml/min per g. Once coronary perfusion was below this critical level, regional shortening in both base to apex and circumferential orientations decreased linearly, depending on the degree of perfusion pressure. Despite the presence of a monoexponential relationship between coronary perfusion pressure or flow and regional shortening, a direct linear relation between perfusion pressure and flow was consistently noted, with or without pulmonary artery banding, suggesting that there is limited autoregulation of right coronary flow. The critical perfusion pressure for maintaining regional myocardial function of the right ventricle was highly dependent on the level of right ventricular systolic pressure (r = 0.64 - 0.72, P < 0.05). Thus, right ventricular systolic pressure was one of the important determinants of regional wall motion during coronary underperfusion.

Coronary Disease Morphology and Distribution Determined by Quantitative Angiography and Intravascular Ultrasound

Although previous studies have demonstrated that even quantitative coronary angiography (QCA) can not provide accurate disease morphology, there has not been a systematic comparison of disease morphology determined by QCA and intravascular ultrasound (IVUS), particularly in Japanese patients. Therefore, the present study prospectively examined patients in a multicenter cooperative study. A total of 491 coronary sites from 562 patients (446 men, 116 women; mean age, 64+/-11 years) who underwent coronary interventions were enrolled. The target lesions (>50% diameter stenosis) were evaluated pre-operatively by both QCA and IVUS operating at 30-40 MHz and the percent area stenosis, eccentricity index (EI) and lesion length were determined. The minimal (min) and maximal (max) distances from the center of the stenotic lesion to the outline of the vessel wall were measured, and the EI was calculated by the formula: [(max - min)/max]. By QCA, lesion length was determined by measuring the distance between the proximal and distal shoulders of the lesion. When the lesions were observed by IVUS with a motorized pull-back system, the length was calculated by multiplying the time for observation of the disease and 0.5 or 1 mm/s. Although the severity of the stenosis determined by QCA (86+/-10%, mean +/- SD) did not differ from that by IVUS (83+/-13%), there was no correlation between them (r=0.32, y=0.25x+65) and the correlation did not improve when lesions with remodeling, enlargement (n=176) or shrinkage (n=79) were omitted from the calculation. The EIs by QCA and IVUS were 0.51+/-0.26 and 0.52+/-0.22, respectively (NS), and there was no correlation between them (r=0.30, y=0.36x+33). However, when the lesions with remodeling were excluded, the correlation greatly improved (r=0.80, y=0.84x+10.6, p<0.05). Lesion length determined by QCA (12.4+/-6.1 mm) was significantly shorter than that by IVUS (16.3+/-8.9 mm, p<0.01). These results demonstrate that coronary angiography significantly misinterprets disease morphology in terms of severity, eccentricity and length, in part because of vessel remodeling that can be accurately determined only by IVUS.

Transmural distribution of myocardial infarction: difference between the right and left ventricles in a canine model.

The evolution of myocardial infarction 24 hours after ligating both the right coronary artery and the obtuse marginal branch of the left circumflex coronary artery was examined in 33 anesthetized dogs. Postmortem coronary angiography and a tracer microsphere technique were used to determine risk areas and their collateral blood flows, respectively. The mean weight of the risk areas was 11.3 ± 0.5 g (mean ± SEM) in the right ventricle and 10.5 ± 0.9 g in the left ventricle (NS). The weight of infarcted tissue was 5.7 ± 0.7 g in the right ventricle and 5.2 ± 0.9 g in the left ventricle (NS). In both ventricles, infarct weight was linearly related to risk area size, and the percent of risk area necrosis was inversely correlated with the extent of collateral flow at 24 hours of coronary ligation, defined as the mean myocardial blood flow inside the central risk area. Ratios of infarct to risk area between the subendocardial and subepicardial layers were 0.76 ± 0.06 and 0.28 ± 0.05 in the right and left ventricles, respectively (p < 0.01, between ventricles, n = 31), which coincided well with subendocardial-to-subepicardial-flow ratios at 24 hours, ie, 0.86 ± 0.04 in the right ventricle and 0.32 ± 0.06 in the left ventricle (p < 0.01). The regional distribution of myocardial infarction correlated well with flow distribution inside the risk area; the slope of these relations was similar between the subendocardium and subepicardium in the right ventricle, whereas in the left ventricle it was larger in the subendocardium than in the subepicardium. Thus, in the dog, the inherent change in the regional distribution of coronary collateral blood flow is an important modifier in the evolution of myocardial infarction, especially in the left ventricle.

Effects of coronary artery occlusion in animals with hypertension and left ventricular hypertrophy.

Chronic arterial hypertension (HT) and left ventricular hypertrophy (LVH) increase the morbidity and mortality of acute myocardial infarction in patients. In this article, we discuss earlier studies from Koyanagi et al. in our laboratory that showed that when animals with chronic HT and LVH (HT-LVH) were subjected to acute coronary artery occlusion (CAO), there was a 3.5-fold increase in mortality and a 35% increase in infarct size expressed as a percent of the area at risk. We subsequently determined the effect of HT-LVH on the wavefront of myocardial infarction. Dogs were made hypertensive using a single-kidney, single-clip model of renovascular hypertension that produced mean arterial blood pressure (BP) = 141 +/- 3 mm Hg and left ventricular:body weight = 5.8 +/- 0.1 g/kg (p less than 0.05 vs. control animals). Conscious animals with HT-LVH and control animals were subjected to 1 or 3 h of CAO. Infarct and risk areas were measured using triphenyltetrazolium chloride (TTC) stain and barium angiography, respectively. The results suggested that the wavefront of infarction was accelerated in animals with HT-LVH. Further studies suggested that the wavefront of myocardial infarction could be markedly retarded by normalizing blood pressure (nitroprusside) 1 h following CAO. Recent studies in an animal model of HT-LVH suggested that electrophysiological abnormalities occur when these animals were subjected to CAO. Sixty-five percent of animals with HT-LVH had sudden death during CAO compared to 27% of the control group. We studied whether chronic beta-adrenergic blockade would reduce mortality associated with CAO in animals with HT-LVH.(ABSTRACT TRUNCATED AT 250 WORDS)