Ventricular Myocardial Necrosis Research Articles

Endothelin antagonist-induced coronary and systemic arteritis in the beagle dog.

Two endothelin antagonists, ZD1611 (3-[4-[3-(3-methoxy-5-methylpyrazin-2-ylsulfamoyl)-2-pyridyl]phenyl]-2,2-dimethylpropanoic acid) and ZD2574 (2-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulfonamide), selective for the ET(A) receptor and intended for use in pulmonary hypertension, were tested in Beagle dogs at various doses for periods of up to 4 weeks. These studies included in vivo telemetric hemodynamic assessment, full histopathological and ultrastructural pathological evaluation of coronary arteries. Both drugs produced arteritis in small- and medium-sized coronary arteries after single or multiple doses, some of which were at or below the ED50. The distribution of lesions was predominantly in extramural arteries over the atria and atrioventricular groove of the right side of the heart and consisted of epicardial hemorrhage and arteritis. Systemic arteritis was also present at a lower incidence than the coronary arteritis, was located at different sites and appeared inconsistently. Ultrastructural changes in coronary arteries suggested that damage was the result of mechanical factors. Although these patterns of vascular injury possessed features in common with those induced in dogs by high doses of vasodilating antihypertensive drugs and inotropic agents, they were atypical, as there was no left ventricular myocardial necrosis, papillary muscle damage, or subendocardial hemorrhage suggestive of ischaemia or excessive inotropism. Moreover, physiological monitoring showed no evidence of exaggerated systemic hypotension or reflex tachycardia at doses associated with vascular damage. Consequently, the changes might be the result of a localized pharmacological process such as intense, prolonged vasodilatation in unsupported arteries that are well endowed with endothelin receptors and particularly sensitive to endothelin antagonism.

Hemodynamic, left ventricular structural and hormonal changes after discrete myocardial damage in the dog

Transmyocardial direct-current (DC) shock produces localized left ventricular myocardial necrosis without obstruction to coronary blood flow. In 43 dogs sequential measurements of hemodynamic, neuroendocrine and myocardial structural changes were made at baseline and for 16 weeks after DC shock. Six dogs (14%) died in the peri-shock period.By 1 week after shock, left ventricular mass, as measured by nuclear magnetic resonance imaging, had increased from a mean value ± SD of 67.9 ± 10.1 to 82.5 ± 12.9 g (p = 0.0001). Left ventricular end-diastolic volume was unchanged at 1 week but increased at 16 weeks from 56.1 ± 10.3 to 70.3 ± 10.7 ml (p = 0.0003). Left ventricular mass demonstrated a further increase at 12 months (107.8 ± 14.8 g). Rest cardiac output was significantly decreased at 4 months (3.67 ± 1.23 to 3.18 ± 0.81 liters/min, p < 0.01) as was stroke volume (43 ± 9 to 37 ± 7 ml, p ≤ 0.01). Left ventricular ejection fraction decreased progressively from 73% to 38% at 1 year. At 4 months there were increases in mean pulmonary artery pressure (18 ± 4 to 23 ± 4 mm Hg, p < 0.01), pulmonary capillary wedge pressure (9 ± 3 to 15 ± 3 mm Kg, p < 0.01) and right atrial pressure (5 ± 4 to 9 ± 3 mm Hg, p < 0.01).Plasma norepinephrine was increased at 4 months (318 ± 190 to 523 ± 221 pg/ml, p = 0.0003), whereas plasma renin activity was not significantly changed (4.3 ± 2.6 vs. 5.2 ± 3.4 ng/ml per h). Microsphere regional blood flow studies demonstrated a 50% reduction in skeletal muscle blood flow at 4 months (0.06 ± 0.06 ml/min per g compared with 0.12 ± 0.09 in normal dogs, p = 0.05), and a reduction in the endocardial/epicardial blood flow ratio (1.11 ± 0.13 compared with 1.24 ± 0.13 in normal dogs, p = 0.02).Therefore, in this model of acute left ventricular damage, left ventricular hypertrophy precedes progressive left ventricular dilation. The hemodynamic and hormonal changes mimic the pattern observed in patients who develop left ventricular dysfunction after myocardial infarction and the model thus provides a unique opportunity to study physiologic and pharmacologic responses during this period.

Atrial standstill, myocarditis and destruction of cardiac conduction system: Clinicopathologic correlation in a dog

A case of permanent atrial standstill is described in a 10-month-old dog with ascites as a presenting complaint. The patient had absence of P waves in all leads in numerous ECG's and had a regular idioventricular rhythm. Pathologically, the patient had multiple areas of atrial and ventricular myocardial necrosis and fibrosis, with chronic active myocarditis and obliteration of the SA and AV node and AV bundle.

Postductal coarctation of aorta causing myocardial ischaemia and heart failure in first week of life.

Two infants with isolated postductal coarctation of the aorta who developed heart failure in the first week of life are reported. Possible factors contributing to symptomatology from this anomaly in the newborn period are discussed. In these two infants there was some evidence that left ventricular myocardial necrosis was an important factor.

Relation of types of dietary fat to cardiovascular damage in mice.

AbstractNine edible oils or fats (hydrogenated coconut, cod liver, Wesson, linseed, olive, butter, lard, corn and cocoa‐butter) were fed for 50–90 days to study the relation of saturation, chain length and essential fatty acid content to production of cardiovascular lesions. The specific oil or fat (selected for ranges in the above variables) was used as the dietary lipid in a high‐fat (28%), low‐protein (8%), hypolipotropic diet. Half of the animals received identical diets containing choline chloride (2 gm/100 gm of diet) as a lipotropic supplement.Atrial mural thrombosis and ventricular myocardial necrosis and calcification developed in all dietary groups. Atrial thrombosis was the most frequent lesion. The greatest incidence of atrial thrombosis occurred in mice fed the choline‐deficient, butter‐containing diet (92%) and the lowest incidence with the supplemented cod liver oil diet (20%). The diet containing unsupplemented hydrogenated coconut oil produced the greatest incidence of ventricular necrosis (79%) and that with choline‐supplemented cocoa‐butter the lowest (8%). Ventricular calcification was most extensive within the unsupplemented cod liver oil group (83%), most limited in the supplemented lard group (5%). In general, choline‐supplemented diets produced a lower incidence of cardiac damage. Little correlation existed between the composition and characteristics of specific fats and their activity in producing the specific cardiac lesions observed here.

Spontaneous and dietary-induced cardiovascular lesions in DBA mice.

AbstractIn DBA mice, 12–16 months of age, receiving an adequate commercial diet the incidence of ventricular myocardial necrosis and calcification was 48% and that of pericardial calcification was 12%. Atrial thrombosis did not occur. Young adult mice of the same strain were fed a high‐fat (28% lard), low‐protein (8% casein) diet, with and without lipotropic supplement of betaine, for 48 weeks. The incidence of ventricular myocardial necrosis and calcification increased significantly over the spontaneous level with the greatest frequency (95%) occurring in the betaine‐supplemented group. Pericardial calcification also increased with the highest incidence (100%) in the non‐supplemented animals. Dietary induced atrial thrombosis reached lethal dimensions (80%) for most animals in the betaine‐supplemented group within 12 weeks. The non‐supplemented animals had less atrial thrombosis (50%) and greater longevity. Frequency and types of lesions observed were similar to those which occur in other strains of mice fed the same diet. The genetic susceptibility to spontaneous cardiac lesions did not appear to predispose the DBA mice to a greater sensitivity to dietary induced lesions, but may have contributed to the calcification which characterized the lesions. Dietary betaine seemed to influence significantly the production of a higher incidence of cardiac damage.