Left Ventricular Hypertrophy Dogs Research Articles

Effects of beta-adrenoceptor stimulation on pacing-induced failure of dog hypertrophic hearts.

1. We tested the hypothesis that the transition to pacing-induced failure in hypertrophic hearts would result in reduced functional and metabolic responses to beta-adrenoceptor stimulation. 2. Isoproterenol (ISO; 0.1 microg/kg per min) was infused into a coronary artery in five anaesthetized open-chest control, five aortic stenosis-induced left ventricular hypertrophy (LVH) and five LVH pacing-induced failure dogs. 3. In both control and LVH dogs, but not in failure dogs, ISO significantly increased local regional work (1,923+/-665 vs 2,656+/-715, 1,185+/-286 vs 1,906+/-562 and 835+/-106 vs 849+/-216g.mm/min, respectively), force (11.1+/-1.4 vs 16.9+/-2.6, 8.6+/-1.5 vs 13.7+/-2.3 and 12.2+/-1.1 vs 11.0+/-1.8g, respectively) and myocardial O2 consumption (7.3+/-2.0 vs 10.0+/-1.5, 8.2+/-1.6 vs 11.6+/-2.6 and 4.4+/-1.5 vs 5.5+/-1.8 mL O2/min per 100 g, respectively). 4. Isoproterenol also significantly increased cAMP in control and LVH dogs (474+/-67 vs 600+/-91 and 473+/-34 vs 619+/-53 pmol/g, respectively). In heart failure, cAMP was significantly lower and there was no significant increase in cAMP in response to ISO (245+/-43 vs 314+/-40pmol/g, respectively). 5. We conclude that there were no significant myocardial functional, O2 consumption or cAMP responses to ISO after the transition from hypertrophy to cardiac failure.

Pacing-Induced Cardiac Failure of Hypertrophic Hearts: Effects of Cyclic GMP Reduction

Background. We tested the hypothesis that pacing-induced cardiac failure of hypertrophic hearts would reduce the functional and metabolic responses of these hearts to guanylate cyclase inhibition and this was associated with alterations in cyclic GMP.Materials and methods. Methylene blue (MB, 2 mg/kg/min, guanylate cyclase inhibitor) was infused into the left anterior descending coronary artery in 5 control, 5 left ventricular hypertrophy (LVH), and 5 LVH pacing-induced failure dogs. Regional myocardial work was calculated as the integrated product of force and segment shortening and regional myocardial O2 consumption (VO2) from coronary blood flow and O2 extraction measurements. Cyclic GMP was determined by radioimmunoassay.Results. MB increased regional work (635 ± 169 vs 1649 ± 500, 781 ± 184 vs 1569 ± 203 g ∗ mm/min) and VO2 (8.3 ± 1.4 vs 10.9 ± 1.4, 7.3 ± 0.7 vs 9.1 ± 0.7 ml O2/min/100 g) in both control and LVH dogs but not in failure dogs (536 ± 234 vs 623 ± 193, 3.6 ± 1.1 vs 4.7 ± 1.9). MB also decreased cyclic GMP in control dogs (1170 ± 142 vs 812 ± 105 pmol/g). LVH dogs had elevated baseline cyclic GMP (5875 ± 949) compared to control dogs but also demonstrated decreased cyclic GMP in response to MB (2820 ± 372). In failure dogs, basal cyclic GMP was also elevated (4650 ± 613) compared to control dogs but there was a lack of response to MB (3670 ± 640).Conclusions. We conclude that the myocardial function, VO2 and cyclic GMP responses to methylene blue are diminished in the transition from hypertrophy to cardiac failure.

DOWN-REGULATION OF beta1-ADRENOCEPTORS IN RAPID PACING-INDUCED HEART FAILURE IN DOGS WITH LEFT VENTRICULAR HYPERTROPHY

Introduction: Experimental left ventricular hypertrophy (LVH) induced by aortic valve stenosis over a 6-month period has been shown to maintain myocardial functions and beta-adrenergic responsiveness, despite a decrease in the density of ventricular beta-adrenoceptors [1]. We studied the underlying mechanism of myocardial decompensation induced by rapid pacing in dogs with LVH. Methods: Pressure overload LVH was created using aortic valve plication in dogs over a 6-month period. Five months after aortic valve plication, congestive heart faiulre (LVH+CHF) was induced by rapid pacing at 240 bpm for 4 weeks. In 5 control, 5 LVH and 5 LVH+CHF anesthetized open-chest dogs, EKG, LV and aortic pressures, segmental length and force were continuously monitored. Isoproterenol was infused into LAD artery over 10 min (0.1 [micro sign]g/kg/min). Partially purified membrane was prepared from a transmural sample from the circumflex region. beta1-adrenoceptors binding studies were carried out using [(125) I] iodocyanopindolol (1.6 - 100 rho M) for total binding and beta1-specific antagonist, esmolol (50 [micro sign]M), for nonspecific binding. The density and affinity of the receptors were determined using Scatchard analysis. ANOVA was used. A value of p<0.05 was accepted as significant. Data were presented as Mean +/- S.E.M. Results: In control and LVH dogs, all baseline hemodynamics and regional mechanimics were similar, except that LVH dogs had a higher LV systolic pressure (167 +/- 11 mm Hg) when compared with controls (119 +/- 9). In LVH+CHF dogs, most baseline hemodynamics were lower than control and LVH dogs, except that LV diastolic pressure (14 +/- 1 mm Hg) was significantly higher than those of control (5 +/- 0) and LVH (5 +/- 1) dogs. Isoproterenol infusion into LAD caused significant increases in LV dP/dt (mm Hg/sec) and regional peak force (g) in control dogs (2839 +/- 481 to 5809 +/- 910; 11.1 +/- 1.4 to 16.9 +/- 2.6) and LVH dogs (3235 +/- 403 to 6010 +/- 607; 8.6 +/- 1.5 to 13.7 +/- 2.3). On the other hand, isoproterenol did not cause significant changes in these parameters in LVH+CHF dogs (1082 +/- 230 to 1480 +/- 210; 12.2 +/- 1.1 to 11 +/- 1.8). The density of myocardial beta1-adrenoceptors (fmol/mg membrane protein; fmol/gm wet tissue) was significantly lower in LVH+CHF dogs (170 +/- 23; 646 +/- 83) when compared to those of control (329 +/- 64; 1601 +/- 216) and LVH (295 +/- 46; 1615 +/- 158) dogs. The receptor affinities were not significantly different among all 3 groups. Discussion: Down-regulation of beta1-adrenoceptors appears to be responsible for the decreased myocardial functions and responses to beta-adrenergic stimulation in the decompensated hypertrophic hearts induced by rapid pacing. Other defects in the receptor-signal transduction pathway may also contribute to cardiac failure.

Diastolic properties in canine hypertensive left ventricular hypertrophy: Effects of angiotensin converting enzyme inhibition and angiotensin II type-1 receptor blockade

Angiotensin II has been suggested to be involved in the pathogenesis of diastolic dysfunction in left ventricular hypertrophy (LVH). The purpose of this study was to asses the effects of enalaprilat and L-158,809, an angiotensin II type-1 receptor antagonist, on LV diastolic function in 16 normal control dogs and 20 LVH dogs with perinephritic hypertension. LV hemodynamics was studied before and after intravenous injection of enalaprilat (0.25 mg/kg) or L-158,809 (0.3 mg/kg). The hemodynamic data were analyzed in relation to the changes in myocardial blood flow (measured by radioactive microspheres) and in the circulating angiotensin II and norepinephrine levels. At baseline, significant increases were observed for LV/body weight ratio as well as LV systolic and end-diastolic pressure in the LVH dogs (all P < 0.01 vs. the control group). In addition, LV relaxation time constant was prolonged and the chamber and myocardial stiffness constants were increased (P < 0.01) in the LVH dogs, suggesting an impairment of LV diastolic function. Administration of enalaprilat or L-158,809 improved LV stiffness constants in the LVH dogs (P < 0.05). The diastolic LV pressure-diameter relation shifted downwards in the LVH dogs whereas diastolic distensibility was not altered in the control dogs. Although the circulating angiotensin II levels were significantly decreased by enalaprilat in the LVH dogs, they did not correlate with the changes in the stiffness constants. Furthermore, the alterations of LV diastolic properties in the LVH group could not be attributed to myocardial perfusion, which was rather decreased by administration of enalaprilat and L-158,809. These results suggest that angiotensin II, particularly at the local level, is involved in the pathogenesis of diastolic dysfunction in pressure-overload LVH. The data also support the concept that ACE inhibitors and angiotensin II receptor blockers are potentially beneficial in the treatment of the hypertrophied heart.

Increased guanylate cyclase activity is associated with an increase in cyclic guanosine 3',5'-monophosphate in left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) produced by aortic valve plication leads to increased myocardial cyclic GMP. We tested whether this was a result of increased soluble guanylate cyclase activity or nitric oxide (NO) synthase and its functional consequences. We used the nitric oxide donor 3-morpholino-sydnonimine (SIN-1) or the NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME) in 12 control and 12 LVH anesthetized open-chest mongrel dogs. L-NAME (6 mg/kg) or SIN-1 (1 microgram/kg per min) was infused into the left anterior descending coronary artery and regional segment work and cyclic GMP levels were determined. In vitro myocardial guanylate cyclase sensitivity (0.43 +/- 0.04 to 0.28 +/- 0.04 mM [EC50]) and maximal activity (10.1 +/- 2.9 to 25.5 +/- 6.5 pmol/mg protein per min) were significantly increased in LVH as compared with control animals in response to nitroprusside stimulation, but cyclic GMP-phosphodiesterase activity was similar. In LVH dogs, basal cyclic GMP was significantly elevated in vivo when compared with controls. Treatment of dogs with SIN-1 resulted in a significant increase in cyclic GMP in control (1.09 +/- 0.12 to 1.48 +/- 0.19 pmol/gram) and a greater increase in the LVH group (1.78 +/- 0.16 to 3.58 +/- 0.71 pmol/g). L-NAME had no effect on myocardial cyclic GMP levels in control or LVH dogs. Segment work decreased in the control group after SIN-1 (1,573 +/- 290 to 855 +/- 211 grams x mm/min). LVH dogs showed no decrement in work as a result of treatment with SIN-1. L-NAME did not cause significant changes in myocardial cyclic GMP, O2 consumption, or work in either control or LVH dogs, but vascular effects were evident. SIN-1 increased cyclic GMP, and with greater effect on LVH; however, this resulted in a decrement in function only in the control group. The greater increased cyclic GMP in LVH dogs is not related to increased NO production, but is related to significantly higher sensitivity and maximal activity of soluble myocardial guanylate cyclase.

Effect of exercise on coronary pressure-flow relationship in hypertrophied left ventricle.

Left ventricular (LV) hypertrophy (LVH) secondary to chronic pressure overload is associated with increased susceptibility to myocardial hypoperfusion and ischemia during exercise. The present study was performed to determine whether exercise causes alterations in minimum coronary resistance or effective back pressure [coronary pressure at zero flow (Pzf)] that limit maximum myocardial perfusion in the hypertrophied heart. Ascending aortic banding in 7 dogs increased the LV weight-to-body weight ratio to 7.7 +/- 0.3 g/kg compared with 4.6 +/- 0.2 g/kg in 11 normal dogs (P < 0.01). Maximum coronary vasodilation was produced by intracoronary infusion of adenosine. Under resting conditions, the slope of the pressure-flow relationship (conductance) was significantly lower in the LVH animals than in the normal dogs (7.2 +/- 0.8 vs. 11.9 +/- 0.8 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01); the slope correlated with the degree of hypertrophy r = 0.74; P < 0.001). The Pzf measured during total coronary artery occlusion (Pzf,measured) was significantly elevated in LVH compared with normal dogs (25.6 +/- 2.2 vs. 13.0 +/- 1.2 mmHg; P < 0.01); Pzf,measured was positively correlated (r = 0.78, P < 0.0005) with LV end-diastolic pressure measured during total coronary artery occlusion (9.0 +/- 1.1 mmHg in normal dogs and 22.2 +/- 3.2 mmHg in LVH dogs; P < 0.01). Graded treadmill exercise to maximum heart rates of 210 +/- 9 and 201 +/- 8 beats/min in normal and LVH animals, respectively, caused similar decreases in the slope of the pressure-flow relationship in LVH (from 7.7 +/- 0.9 to 6.1 +/- 0.8 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01) and normal dogs (from 11.9 +/- 0.8 to 10.0 +/- 0.7 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01). However, exercise-induced increases in Pzf,measured were significantly greater in the LVH animals (from 25.6 +/- 2.2 to 40.8 +/- 2.1 mmHg; P < 0.01) than in normal animals (from 13.0 +/- 1.2 to 24 +/- 2.1 mmHg; P < 0.01) (P < 0.01 LVH vs. normal). The greater increase in Pzf paralleled a more pronounced increase in LV end-diastolic pressure in the LVH dogs from 22.2 +/- 3.2 to 39.1 +/- 2.7 mmHg) than in normal dogs from 9.0 +/- 1.1 to 14.2 +/- 2.0 mmHg). The results suggest that exaggerated increases in filling pressure during exercise in the hypertrophied left ventricles contributed to impairment of myocardial perfusion during exercise by augmenting the back pressure, which opposes coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship between cyclic-AMP content, regional myocardial function and O 2 consumption in experimental left ventricular hypertrophy: Effect of negative inotropes

The aim of this study was to examine the hypothesis that negative inotropic agents that lower myocyte cyclic-AMP by different means would have similar effects on local myocardial segment work and O 2 consumption in control hearts, but that this response would differ in left ventricular hypertrophy (LVH) induced by aortic valve stenosis. Open chest anesthetized LVH and control dogs were studied before and during esmolol (100 μg/kg/min) and acetylcholine (100 μg/kg/min) infusion. Regional work was calculated as the integrated product of instantaneous force (miniature transducer) and shortening (sonomicrometry) per min. Regional O 2 consumption was calculated from blood flow (radioactive microspheres) and O 2 saturation of small frozen vessels (microspectrophotometry). Cyclic-AMP level was determined with a competitive binding assay using 3H-cyclic-AMP and was found to be 731 ± 90 (mean ± S.D.) pmol/g in control and 711 ± 163 in LVH. There were similar decreases in cyclic-AMP levels in control hearts with acetylcholine (365 ± 135) and the beta adrenergic blocker (430 ± 95). In LVH, esmolol lowered cyclic-AMP (383 ± 39), but acetylcholine did not (689 ± 105). In control animals, regional O 2 consumption (7.7 ± 0.6, 5.6 ± 0.4 and 5.6 ± 0.5 ml O 2/min/100 g, control, acetylcholine, esmolol, respectively) and segment work ( 878 ± 82, 546 ± 80, 627 ± 66 g ∗mm/min ) fell to similar levels with these agents. Similar decreases were found in LVH with esmolol for O 2, consumption (7.1 ± 1.2, 5.1 ± 1.0, baseline, esmolol) and segment work (895 ± 140, 427 ± 65). Acetylcholine had no significant effect on segment work (800 ± 201), but did lower regional O 2 consumption (4.0 ± 0.7) in LVH dogs. It is concluded that there is a strong relationship between the level of cyclic-AMP and myocardial function and O 2 consumption in control hearts. The action of acetylcholine is altered in LVH leading to an uncoupling between regional cyclic-AMP, function and metabolism.

Capillary growth and geometry during long-term hypertension and myocardial hypertrophy in dogs

Angiogenic response of the myocardial capillary bed to long-term (7 mo) renovascular hypertension (one-kidney, one-clip) was assessed in eight mongrel dogs and compared with seven control dogs. Image analyses of histological sections from four transmural specimen sites of left ventricular (LV) free wall were performed. While mean cross-sectional cardiocyte area increased in all transmural layers (epi-endo) in dogs with LV hypertrophy (LVH), the greatest increases occurred in the inner layers. Although capillary length density was significantly lower in two of the four transmural regions of LVH dogs, these decrements were much less than the lateral expansion of cardiocytes as indicated by cross-sectional areas. Calculations of total capillary length indicate that approximately one-fifth of the capillary bed in LVH dogs was formed during the 7-mo period of hypertension in hypertrophied hearts. Capillary volume and surface densities in LVH dogs decreased to a greater extent due to a larger population of capillaries with lumen diameters less than 4 microns. Capillary volume density in LVH dogs was remarkably similar across the wall despite large transmural differences in cardiocyte hypertrophy. LVH did not alter the log SD of capillary domains, a measure of the heterogeneity of spacing, or capillary orientation (degree or anisotropy). These data support several important conclusions regarding long-term hypertension-induced LVH in dogs. First, although capillary growth does not fully compensate for the increase in LV mass, a myriad of new capillaries are formed as indicated by a substantial increase in total capillary length. This growth minimizes the increase in intercapillary distance characteristic of LVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of coronary stenosis on myocardial blood flow during exercise in the chronically pressure-overloaded hypertrophied left ventricle.

This study was performed to determine if a coronary artery stenosis would result in more-severe perfusion abnormalities in hypertrophied compared with normal canine hearts during exercise. Studies were performed in eight normal control dogs and in seven adult dogs in which a 67% increase in left ventricular mass wa produced by banding the ascending aorta at 9 weeks of age. Myocardial blood flow was measured by the microsphere method during treadmill exercise in the presence of a coronary artery stenosis that decreased distal coronary perfusion pressure to 55 or 42 mm Hg. At a coronary pressure of 55 mm Hg, mean myocardial blood flow was decreased by 23 +/- 5% in normal control dogs but was decreased by 53 +/- 10% in dogs with left ventricular hypertrophy (LVH) (p less than 0.05, comparing normal vs. LVH dogs). Similarly, at a coronary pressure of 42 mm Hg, mean blood flow was decreased by 53 +/- 6% below control in normal dogs but was decreased by 76 +/- 5% below control values in dogs with LVH (p less than 0.01, comparing normal vs. LVH dogs). In both groups of dogs, the stenosis caused a gradient of hypoperfusion, worsening from epicardium to endocardium. However, for each level of stenosis, subendocardial blood flow and the ratio of subendocardial to subepicardial blood flow was less in LVH than in normal canine hearts. These findings demonstrate that the presence of LVH secondary to long-term pressure overload is associated with an increased vulnerability to myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis.

Exercise-induced subendocardial dysfunction in dogs with left ventricular hypertrophy.

The effects of treadmill exercise on regional myocardial blood flow and function were examined in 10 adult, conscious dogs with left ventricular hypertrophy (LVH) induced by aortic banding in puppies, which resulted in a left ventricular (LV) weight/body weight ratio of 8.5 +/- 0.3. Data were compared with results from eight control dogs with an LV weight/body weight ratio of 4.9 +/- 0.2. At rest, LV systolic and end-diastolic pressures were significantly greater (p less than 0.01), and mean arterial pressure was significantly less (p less than 0.05) in LVH dogs. Mean myocardial blood flow (control dogs, 0.98 +/- 0.11 ml/min/g; LVH dogs, 1.16 +/- 0.06 ml/min/g) and the transmural blood flow distribution at baseline, as assessed by endocardial/epicardial blood flow ratio (control, 1.35 +/- 0.12; LVH, 1.21 +/- 0.09), were similar in the two groups. During exercise to a target heart rate (240 beats/min), LVH dogs demonstrated greater (p less than 0.01) increases in LV systolic and end-diastolic pressures. In control dogs, as expected, exercise augmented velocity of circumferential fiber shortening (16 +/- 9%) and shortening fraction (15 +/- 5%), but in LVH dogs, exercise reduced the velocity of circumferential fiber shortening (-14 +/- 6%) and shortening fraction (-17 +/- 5%). Exercise also increased full wall thickening (35 +/- 5%), subendocardial wall thickening (66 +/- 10%), and subepicardial wall thickening (44 +/- 9%) in control dogs. In LVH dogs, exercise increased subepicardial wall thickening (31 +/- 9%) and reduced subendocardial wall thickening (-40 +/- 7%); full wall thickening did not change (-11 +/- 9%). This was associated with a fall in endocardial/epicardial flow ratio to 0.72 +/- 0.05 (p less than 0.01) in LVH dogs. The subendocardial dysfunction persisted late into recovery, at a time when the transmural blood flow distribution had returned to baseline; this occurrence suggested myocardial stunning. Thus, in dogs with LVH, selective subendocardial hypoperfusion and profound selective depression in subendocardial wall thickening are observed during exercise. The subendocardial dysfunction persisted into recovery despite resolution of the perfusion abnormality.

Blood supply to the heart and coronary vasodilator reserves in experimental myocardial hypertrophy

The effects of pressure overload left ventricular hypertrophy (LVH) on heart performance and coronary circulation were investigated in dog experiments. The data obtained clearly demonstrate that left ventricular systolic and end-diastolic pressures were increased in LVH dogs. The heart rate and cardiac output were unchanged. However, there was a tendency toward lowering in the maximal rate of myocardial contractility and relaxation (+dP/dtmax and--dP/dtmax). It has been shown that in LVH dogs, the coronary blood flow was higher and coronary artery resistance was lower than in control ones. The peak reactive hyperemic flow was higher in LVH dogs but the coronary artery resistance calculated at the height of reactive hyperemia was similar both in control and LVH dogs, evidence of a reduction in the total coronary vasodilator reserves in the latter ones. The diastolic pressure-time index-tension time index (DPTI/TTI) ratio in LVH dogs decreased so that the value was sufficiently low to predict a reduction in endocardial perfusion even in experimental increased coronary perfusion pressure.

Basal and maximal inotropic state in renal hypertensive dogs with cardiac hypertrophy.

We studied three isovolumic indexes of contractility, i.e., dP/dtmax, dP/dtDP40, and (dP/dt)/TPmax, in normal dogs and in a matched group of chronically hypertensive dogs with left ventricular hypertrophy (LVH) [DP40, developed LV pressure of 40 mmHg; TP, total LV pressure above atmospheric]. The LVH was moderate in degree with the LV-to-body weight ratio 50% greater than in normal dogs. The experiments were performed under pentobarbital with open chest, autonomic blockade, and independent control of mean left atrial pressure (LAP) and mean aortic pressure (MAP). We found that dP/dtmax provided the most consistent comparison of inotropic state in the two groups under both basal conditions and with norepinephrine (NE). The other indexes occurred too early in systole to reflect complete LV activation, particularly during the infusion with NE. Under controlled conditions basal dP/dtmax of LVH dogs was 1.28 times the value of normal dogs, with the increase accounted for by the amplifier effect of the increase in LV mass. But with moderate lowering of aortic pressure, inotropic state was more easily compromised in LVH than in normal dogs. With steady-state stimulation by infusing increasing amounts of NE, dP/dtmax rose by 10 times basal in both LVH and normal dogs at maximum stimulation. The absolute value of the index was 1.31 times higher in the LVH group, with the amplifier effect thus the same as under basal conditions. The results suggest that basal and maximal inotropic states are normal in LVH under optimum loading conditions.

Effect of ischemia, hypertrophy, hypoxia, acidosis, and alkalosis on canine defibrillation.

Our purpose was to assess the effect of myocardial ischemia, left ventricular hypertrophy, and systemic hypoxia and acid-base abnormalities on the energy requirements for defibrillation. We determined the defibrillation threshold (DFT), the minimum energy required to defibrillate. DFT was not significantly elevated after left anterior descending coronary occlusion, nor was there a relationship between the size of the occluded coronary distribution area (coronary risk area) and the change in DFT in individual animals. Renal hypertension and left ventricular hypertrophy were induced by unilateral nephrectomy and contralateral renal artery stenosis. DFT in left ventricular hypertrophy dogs was not significantly higher than in dogs without hypertrophy. Finally, we induced systemic hypoxia and acid-base abnormalities. Neither respiratory nor metabolic acid-base disturbances affected DFT, but during systemic hypoxia (O2 tension 45 +/- 2) DFT fell from 83 +/- 49 to 58 +/- 28 J (P less than 0.01). Thus in dogs, myocardial ischemia, left ventricular hypertrophy, and acid-base abnormalities do not elevate defibrillation energy requirements, whereas hypoxia reduces the energy needed to defibrillate.

Regional myocardial blood flow in left ventricular hypertrophy: An experimental investigation in Newfoundland dogs with congenital subaortic stenosis

To test the hypothesis that left ventricular hypertrophy (LVH) may predispose the subendocardium to ischemia, we studied regional myocardial blood flow in dogs with the fibrous ring form of subvalvular aortic stenosis and concentric LVH. Radioactive microspheres, 9 +/- 1 mu in diameter, were used. Eleven dogs with LVH (left ventricular body weight ratio of 6.35 +/- 0.46 gm/kg [mean +/- SEM] and peak left ventricular outflow gradient of 51 +/- 7 mm Hg) were compared to 12 normal dogs (left ventricular/body weight ratio of 3.41 +/- 0.12 gm/kg and peak left ventricular outflow gradient of 6 +/- 3 mm Hg). The two groups of dogs were subjected to comparable experimental interventions including (1) tachycardia produced by atrial pacing (221 +/- 4 beats/min), (2) ascending aortic constriction producing systolic hypertension (212 +/- 5 mm Hg), and (3) creation of an aortic-right atrial fistula lowering diastolic blood pressure (38 +/- 3 mm Hg). Basal regional myocardial blood flow was distributed similarly for LVH and normal dogs (endocardial/epicardial ratio = 0.90 +/- 0.05 and 0.94 +/- 0.03, respectively). During experimental interventions, regional blood flow remained equal to all myocardial layers in normal dogs; however, the endocardial/epicardial ratio diminished in LVH dogs during atrial tachycardia to 0.61 +/- 0.08, during systolic hypertension to 0.68 +/- 0.06, and during diastolic hypotension to 0.50 +/- 0.09. When the diastolic/systolic pressure time index ratio (DPTI/SPTI) was less than 0.8, subendocardial ischemia occurred in dogs with LVH (endocardial/epicardial ratio = 0.66 +/- 0.04) but not in normal dogs (endocardial/epicardial ratio = 0.92 +/- 0.03) (p less than 0.0001). Animals with infracoronary obstruction and LVH demonstrate greater susceptibility to development of subendocardial ischemia for identical hemodynamic interventions than do normal animals.

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 less than 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 less than 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 less than 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.

Maximum contractility of the experimentally hypertrophied heart in situ and survival of the acute coronary occlusion.

Studies were carried out in dogs with significant moderate left ventricular hypertrophy (LVH) induced by artifical coarctatio aortae to reveal the reserve of performance and the behavior in response to acute ligation of the LCA (left circumflex artery). The hemodynamic data at rest and during catecholamine stimulation were not essentially different, whereas the maximal inotropic state was a little enhanced in LVH dogs (LVH1 = 12; CG1 = 6). The acute maximal pressure rise of the left ventricle — obtained by acute clamping of the aorta ascendens — was nearly the same in both groups (LVH2 = 6; CG2 = 6) when related to 100 g left ventricular wet weight. The LVH hearts react to a rapid volume overload with a slightly higher increase of HR and LVEP indicating a minor adaption to an acute volume overload explained by diminished compliance. In consequence to acute ligation of the LCA (LVH3 = 13; CG3 = 11) LVH hearts showed a higher (p < 0.05) survival rate (69%) than controls with comparable collateral status of the coronary collateral vessels because 91% of these developed ventricular fibrillation. To explain this phenomenon we determined the catecholamine-concentration in each part of the heart in a further group (LVH4 = 5; CG4 = 6). Unexpectedly a significant diminution was seen in the non-hypertrophied right ventricle, but the other compartments also showed a decrease of the catecholamine concentration. Subsequent studies have to be done to explore the better electrophysiologic protection of the LVH heart in consequence to acute ligation of the LCA.