Ventricular Free Wall Weight Research Articles

Binucleated Myocytes and Heart Weight: A Preliminary Study Linking Cardiac Hypertrophy and Myocyte Hypertrophy.

Hypertrophy of the heart is assessed by heart weight (and dimensions) and myocyte hypertrophy. Establishing an association between the two may be useful in assessing hypertrophy in cases where there are limitations in assessing the heart weight. This preliminary study explored the association between the number of binucleated myocytes (a feature of myocyte hypertrophy) in a randomly chosen single high-power field of the left ventricular free wall and heart weight in an adult White population. It also compared the number of binucleated myocytes between cases with increased heart weight (>400 g in female and >500 g in male) and cases with normal heart weight. Heart weight and number of binucleated myocytes correlated significantly in male only. Increased heart weight had a significantly higher number of binucleated myocytes, with 8.5 binucleated myocytes being able to segregate cases with increased heart weight (74% sensitivity and 79% specificity). The results of this study showed the number of binucleated myocytes may have a complementary role in assessing hypertrophy of the heart.

SU5416 plus hypoxia but not selective VEGFR2 inhibition with cabozantinib plus hypoxia induces pulmonary hypertension in rats: potential role of BMPR2 signaling.

SU5416 plus chronic hypoxia causes pulmonary arterial hypertension in rats and is assumed to occur through VEGFR2 inhibition. Cabozantinib is a far more potent VEGFR2 inhibitor than SU5416. Therefore, we hypothesized that cabozantinib plus hypoxia would induce severe pulmonary arterial hypertension in rats. Cell proliferation and pharmacokinetic studies were performed. Rats were given SU5416 or cabozantinib subcutaneously or via osmotic pump and kept hypoxic for three weeks. Right ventricular systolic pressure and hypertrophy were evaluated at days 14 and 28 following removal from hypoxia. Right ventricular fibrosis was evaluated with Picro-Sirius Red staining. Kinome inhibition profiles of SU5416 and cabozantinib were performed. Inhibitor binding constants of SU5416 and cabozantinib for BMPR2 were determined and Nanostring analyses of lung mRNA were performed. Cabozantinib was a more potent VEGFR inhibitor than SU5416 and had a longer half-life in rats. Cabozantinib subcutaneous plus hypoxia did not induce severe pulmonary arterial hypertension. Right ventricular systolic pressure at 14 and 28 days post-hypoxia was 36.8 ± 2.3 mmHg and 36.2 ± 3.4 mmHg, respectively, versus 27.5 ± 1.5 mmHg in normal controls. For cabozantinib given by osmotic pump during hypoxia, right ventricular systolic pressure was 40.0 ± 3.1 mmHg at 14 days and 27.9 ± 1.9 mmHg at 28 days post-hypoxia. SU5416 plus hypoxia induced severe pulmonary arterial hypertension (right ventricular systolic pressure 61.9 ± 6.1 mmHg and 64.9 ± 8.4 mmHg at 14 and 28 days post-hypoxia, respectively). Cabozantinib induced less right ventricular hypertrophy (right ventricular free wall weight/(left ventricular free wall weight + interventricular septum weight) at 14 days post-hypoxia compared to SU5416. Right ventricular fibrosis was more extensive in the SU5416 groups compared to the cabozantinib groups. SU5416 (but not cabozantinib) inhibited BMPR2. Nanostring analyses showed effects on pulmonary gene expression of BMP10 and VEGFR1 in the SU5416 28 days post-hypoxia group. In conclusion, selective VEGFR2 inhibition using cabozantinib plus hypoxia did not induce severe pulmonary arterial hypertension. Severe pulmonary arterial hypertension due to SU5416 plus hypoxia may be due to combined VEGFR2 and BMPR2 inhibition.

RETRACTED: Influence of gestational overfeeding on myocardial proinflammatory mediators in fetal sheep heart

Maternal overnutrition is associated with predisposition of offspring to cardiovascular disease in later life. Since maternal overnutrition may promote fetal and placental inflammatory responses, we hypothesized that maternal overnutrition/obesity increases expression of fetal cardiac proinflammatory mediators and alter cardiac morphometry. Multiparous ewes were fed either 150% of National Research Council (NRC) nutrient recommendations (overfed) or 100% of NRC requirement (control) from 60 days prior to mating to gestation Day 75 (D75), when ewes were euthanized. An additional cohort of overfed and control ewes were necropsied on D135. Cardiac morphometry, histology, mRNA and protein expression of toll-like receptor 4, iNOS, IL-1a, IL-1b, IL-6, IL-18, CD-14, CD-68, M-CSF and protein levels of phosphorylated I-κB and nuclear factor κB (NF-κB) were examined. Immunohistochemistry was performed to assess neutrophil and monocyte infiltration. Crown rump length, left and right ventricular free wall weights as well as left and right ventricular wall thickness were significantly increased in D75 fetuses of overfed mothers. Hematoxylin and eosin staining revealed irregular myofiber orientation and increased interstitial space in fetal ventricular tissues born to overfed mothers. Oil red O staining exhibited marked lipid droplet accumulation in the overfed fetuses. Overfeeding significantly enhanced TLR4, IL-1a, IL-1b IL-6 expression, promoted phosphorylation of IκB, decreased cytoplasmic NF-κB levels and increased neutrophil and monocyte infiltration. Collectively, these data suggest that maternal overfeeding prior to and throughout gestation leads to inflammation in the fetal heart and alters fetal cardiac morphometry.

Influence of gestational overfeeding on cardiac morphometry and hypertrophic protein markers in fetal sheep

Intrauterine overnutrition is associated with development of cardiovascular disease in adulthood although the underlying mechanism has not been precisely elucidated. This study evaluated the effects of maternal overnutrition on fetal cardiac morphometry and hypertrophy-related mRNA/protein expression. Multiparous ewes were fed either 150% of National Research Council (NRC) nutrient requirements (overfed group) or 100% of NRC requirements (control group) from 60 days before mating to Day 75 (D75) of gestation, when ewes were euthanized. Cardiac morphometry, histology and expression of Akt, forkhead-3a (Foxo3a), glycogen synthase kinase-3β (GSK3β), mammalian target of rapamycin (mTOR), NFATc3 and GATA4, atrial natriuretic factor (ANF), calcineurin A and caspase-8 were examined. Crown rump length, left and right ventricular free wall weights and left ventricular wall thickness were increased in D75 overnourished fetuses. Hematoxylin and eosin staining revealed irregular myofiber orientation and increased interstitial space in heart tissues from overfed group. Masson's trichrome staining displayed myofiber hypertrophy and fascicular disarray in heart tissues from overfed group. Overfeeding significantly enhanced Foxo3a phosphorylation in both ventricles, while protein expression of Akt, Foxo3a, GSK3β and caspase-8 as well as phosphorylated Akt and GSK3β in either ventricle was unaffected. Overfeeding increased left ventricular mTOR, NFATc3 (both total and phosphorylated) and calcineurin A. GATA4, pGATA4 and ANF expression were unchanged in both ventricles. Collectively, our data suggested that overfeeding during early to mid gestation (D75) leads to morphometric changes without overt pathology which may be related to elevated expression of mTOR, NFATc3, calcineurin A and phosphorylation of Foxo3a, mTOR and NFATc3.

Changes in myosin heavy chain and its localization in rat heart in association with hypobaric hypoxia-induced pulmonary hypertension.

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodelling of the heart. In rat cardiac ventricles, pressure and volume overload are well known to be associated with changes in cardiac myosin heavy chain (MHC) isoforms. To study the effects of HHE on the MHC profile in the ventricles, 83 male Wistar rats were housed in a chamber at the equivalent of 5500 m altitude for 1-8 weeks. Pulmonary arterial pressure, right ventricular free wall (RVFW) weight, the ratio of RVFW weight over body weight (BW), the ratio of left ventricular free wall (LVFW) weight over BW, and myocyte diameter in both ventricles showed significant increases after 1 week, 2 weeks, 1 week, 6 weeks, and 4 weeks of HHE, respectively. Semi-quantitative reverse transcriptase-polymerase chain reaction revealed that beta-MHC mRNA expression was increased significantly in both ventricles at 6 and 8 weeks of HHE, whereas alpha-MHC mRNA expression was decreased significantly at 6 and 8 weeks of HHE in the right ventricle (RV) and at 6 weeks of HHE in the left ventricle (LV). The percentage of myosin containing the beta-MHC isoform was increased significantly at 4-8 weeks of HHE in RV and at 6 weeks of HHE in LV. In situ hybridization showed that the area of strong staining for beta-MHC mRNA was increased in both ventricles at 8 weeks of HHE, and showed a decrease from RVFW to cardiac septum, and from cardiac septum to LVFW. These results suggest that HHE has a significant effect on the expression of both MHC mRNA and protein in the heart, particularly in RV. These changes may reflect a role for cardiac MHC in the response to pulmonary hypertension in HHE.

Right ventricular mass measurement by electron beam computed tomography. Validation with autopsy data.

Validation of right ventricular mass quantitation by electron beam computed tomography in humans has not been performed. The ability of electron beam computed tomography to accurately determine the septal component of the right ventricle also has not been determined. This article addresses both issues. Twenty human adult hearts obtained at autopsy were scanned by electron beam computed tomography in a short-axis projection. Planimetry of the right ventricular free wall and septal components of each slice was performed and summed to determine right ventricular mass. These measurements were compared against comparable measurements obtained by autopsy weights of the hearts. Right ventricular free wall weights by electron beam computed tomography (53.9 +/- 18.4 g) correlated well (slope = .92, r = .92, standard error of the estimate = 7.4 g, P < .001) with autopsy weights (55.8 +/- 18.4 g). Right ventricular septal weights by electron beam computed tomography (6.1 +/- 2.3 g) correlated poorly (slope = .04, r = .11, standard error of the estimate = 2.4 g, P = .65) with autopsy weights (13.9 +/- 6.3 g). Electron beam computed tomography quantitation of right ventricular mass is accurate in humans if only the free wall and not the septal component is utilized.

Pulmonary hypertension and vascular remodeling in fetal sheep.

Vascular remodeling is commonly associated with pulmonary hypertension (PH) postnatally, but little is known about its presence in fetuses. In sixteen fetal sheep (126 wk gestation), the ductus arteriosus (DA) was ligated, and the animals were studied at 4, 8, and 14 days after surgery. The uninstrumented twins served as controls. Four days post-DA ligation PH resulted in an increase in the right and left ventricular free wall weight ratio (1.2 +/- 0.1 vs. 1.0 +/- 0.1 in the controls; P < 0.01), with a further progressive increase at 8 (1.4 +/- 0.1 vs. 1.0 +/- 0.1; P < 0.01) and 14 days (1.5 +/- 0.2 vs. 1.0 +/- 0.1; P < 0.01). An increase in vascular percent medial thickness was observed after 4 days of DA ligation and was restricted to small vessels. The large arteries collagen and elastin contents were 28.9 +/- 3.4 and 27.1 +/- 3.4 micrograms/micrograms of DNA, respectively, and were not significantly different from control values even after 14 days DA ligation. We further compared elastin synthesis in fetal and neonatal arteries in vitro. Synthesis in the fetus was greater than the newborn (10.6 +/- 1.4 vs. 4.6 +/- 0.7 cpm.mg wet wt-1.h-1; P < 0.01). Vessel endothelium denudation reduced synthesis to 60 +/- 8% of controls in the fetus, whereas no change was seen in the newborn. After an increase in wall stress, synthesis increased in the fetus (194 +/- 28% of control P < 0.01) and newborn (173 +/- 25%; P < 0.01). Removal of the endothelium abolished the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal ductus arteriosus ligation. Pulmonary vascular smooth muscle biochemical and mechanical changes.

To evaluate the smooth muscle mechanical and biochemical changes associated with persistent pulmonary hypertension syndrome of the newborn, we studied 31 fetal sheep in which the ductus arteriosus was ligated at 125 days of gestation. Sixty-one noninstrumented and six sham-operated fetuses served as controls. All animals were delivered by cesarean section at 137-140 days of gestation, and the experimental group had the ductus arteriosus ligated for 12 +/- 3 days. The ligated group demonstrated a higher mean (+/- SEM) pulmonary artery pressure (72.3 +/- 3.8 versus 54.1 +/- 2 mm Hg, p < 0.01) and right ventricular mean free wall weight (12.5 +/- 0.7 versus 6.8 +/- 0.3 g, p < 0.01) as compared with the sham-operated group. Significant changes in the pulmonary vascular smooth muscle of the ligated group were observed. The myosin content of vessels from the second through fifth generation demonstrated a significant increase in actin and myosin content (p < 0.01), but given their disproportional changes, the noninstrumented group demonstrated a lower actin/myosin ratio than the experimental group (p < 0.01). Changes in the myosin heavy chain isoform stoichiometry, characterized by an increase in both the mean high/low myosin heavy chain isoform ratio (1.8 +/- 0.3 versus 1.0 +/- 0.1, p < 0.05) and the nonmuscle isoform as a percentage of the total myosin heavy chain (12.4 +/- 0.7% versus 2.7 +/- 0.9%, p < 0.01), were also observed in the ligated as compared with the noninstrumented animals. In addition, the muscle Mg-ATPase activity was significantly (p < 0.05) reduced in the experimental group.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamics of heartworm infection.

To determine the hemodynamic responsiveness of dogs testing positive for heartworms (direct blood smear), we compared the response of control and heartworm-infected animals to stellate stimulation (SS). Using the anesthetized, open-chest model, twenty dogs (10 control and 10 heartworm-positive) were instrumented to measure left ventricular pressure (LVP), arterial pressure (AP), and coronary flow velocity (CFV) of the left circumflex coronary artery. CFV was converted to flow per gram tissue (CBFG) by weighing the perfusion area of the circumflex artery. The average wet weight of the worm mass infecting the dogs was 1.0 +/- 0.1 g, which represented an average of 5% of the right ventricular free wall weight. Overall heart size and right ventricular weights were greater in the heartworm-positive animals, as well as heart weight to body weight ratios. Prior to SS, LVP was the same for both groups. However, dP/dt and CBFG were 21% and 19% lower, respectively, in the heartworm-positive animals. Stellate stimulation sufficient to produce a 30-mmHg rise in AP led to 25%, 13%, and 40% increases in LVP, dP/dt, and CBFG, respectively, in the control animals. Increases of 22%, 10%, and 52% in the same parameters were observed in the heartworm-positive animals. Although control dP/dt and CBFG in the heartworm-positive animals were lower than in the heartworm-negative animals, heartworm infection at this level did not hinder myocardial responsiveness to SS.

Mild pressure loading alters right ventricular function in fetal sheep.

Right ventricular function before and during 10 days of mild pressure loading (10 mm Hg increase in mean pulmonary arterial pressure) was compared with right ventricular function in unloaded near-term fetal sheep. Pressure loading did not alter fetal arterial blood gases or vascular pressures. The right ventricular function curve (stroke volume versus mean right atrial pressure) was not significantly altered by loading. However, the relation between right ventricular stroke volume and increased arterial pressure was dramatically shifted upward, indicating improved ventricular function after the 10-day loading period. Normalized free wall of the loaded right ventricles became thicker (1.2 +/- 0.2 versus 0.9 +/- 0.2 mm/kg, p less than 0.01) and heavier (2.7 +/- 0.4 g/kg versus 2.2 +/- 0.4 g/kg, p less than 0.05) than control, and the ratio of the equatorial radius of curvature to wall thickness decreased (3.2 +/- 0.5 versus 4.5 +/- 0.9, p less than 0.005). Left ventricular free wall and septal weights and thicknesses were not significantly changed. The in vitro diastolic pressure-volume curves of both ventricular chambers of loaded hearts shifted to the left, indicating smaller ventricles than controls at physiological filling pressures. These data suggest the transduction of right ventricular loading effects to the left ventricle. Improved right ventricular function after loading is predicted by the law of Laplace based on the decreased radius of curvature-to-wall thickness ratio.

Verapamil induced ventricular hypertrophy in conscious dogs

Verapamil is used clinically in the treatment of various cardiac diseases including hypertrophic cardiomyopathy. Its long term effects on ventricular mass are not well known. In 11 conscious dogs heart rate, aortic and left ventricular pressures, cardiac output, a methoxamine induced stress ventricular function test and left ventriculography were performed. These variables were measured prior to and following a mean 7.2 month infusion of verapamil at 0.005 or 0.01 mg.kg-1.min-1 using a subcutaneously implanted pump. Resting haemodynamic variables and left ventricular ejection fraction [60(SD 6) v 55(6)%] were unchanged between baseline and chronic verapamil studies, but the slope of the methoxamine induced stress ventricular function test decreased from 3.9(0.8) to 2.1 (1.3). After verapamil was discontinued the mean slope of the stress ventricular function test returned to the baseline 4.0(1.7). Total ventricular weight increased 22% from 176.1(17.5) g.m-2 in controls to 215.6(29.5) g.m-2 (p less than 0.01) in the verapamil animals. The right ventricular weight increased 25% from 46(5.9) to 57.6(9.1) g.m-2 (p less than 0.01); the septum weight increased 26% from 42.5(4.1) to 53.7(7.2) g.m-2 (p less than 0.001); and the left ventricular free wall weight increased 19% from 87.4(9.8) to 103.9(15.7) g.m-2 (p less than 0.01). The increase in ventricular weights was not due to fibrosis or oedema since hydroxyproline contents and wet/dry ratios were not increased. In conclusion, a chronic infusion of verapamil in conscious dogs caused no change in resting haemodynamic variables but produced reversible depression of stress ventricular function and biventricular and septal hypertrophy.

A simple model of right ventricular hypertrophy.

Previous models of right ventricular hypertrophy (RVH) created by pulmonary artery (PA) banding in adult large animals have been associated with an unpredictable response of the right ventricle to the band and a high mortality due to the variable degree of acute stenosis. We studied the efficacy of PA banding in young pigs to produce RVH by progressive gradual stenosis during growth. Sixteen Yorkshire pigs at 6 weeks of age had nonconstricting 5-mm wide Dacron strips placed around the PA via a left minithoracotomy. The animals were returned for study in 2-3 months. There were no deaths during the growth period. Five sham-operated pigs acted as controls. Right ventricular free wall (RVFW) to total heart weight ratio was greater in the banded group (0.38 +/- 0.05 vs. 0.28 +/- 0.01, P less than .005) as was the RVFW to left ventricular free wall (LVFW) weight (1.09 +/- 0.25 versus 0.66 +/- 0.03, P less than .005). While the LVFW to total heart weight ratio decreased (0.36 +/- 0.04 vs 0.45 +/- 0.05, P less than .005), the septal ratio did not change (0.26 +/- 0.04 vs. 0.29 +/- 0.02, NS), indicating concomitant septal hypertrophy. This technique is simple, reliable, and reproducible in creating right ventricular and septal hypertrophy in the young pig with no mortality during maturation.

Percutaneously Adjustable Pulmonary Artery Band

Conventional banding techniques result in up to 50% mortality as a result of improper and fixed constriction of the pulmonary artery in patients in unstable condition. We developed a percutaneously adjustable band with a fluid-filled reservoir that allows variable constriction without thoracotomy or other surgical procedures. Six pigs ranging in weight from 7 to 10 kg underwent pulmonary artery banding. Swan-Ganz catheterization, ultrasound studies, and Doppler studies were used to adjust and monitor the pressure gradient across the band. Thirty days after banding, the pigs were killed; their hearts were sectioned, weighed, and compared with hearts from a control group of six pigs weighing 11 to 13 kg. The ratio of mean total heart weight to total body weight (× 10 −3) was 6.3 ± 0.7 in the banded group and 4.4 ± 0.3 in the controls ( p < 0.001). The ratio of left ventricular weight to right ventricular weight was 0.76 ± 0.1 in the banded group and 1.6 ± 0.1 in the controls ( p < 0.001). The thickness of the right ventricular free wall was 4.9 ± 0.5 mm in the banded group and 2.6 ± 0.5 mm in the controls ( p < 0.001). Right ventricular free wall weight in the banded group was 25.9 ± 5.8 gm compared with 11.1 ± 1.3 gm in the controls ( p < 0.001). These results demonstrate the effectiveness of the band in inducing right ventricular hypertrophy. Since the band is easily placed and simply adjusted percutaneously, this device promises to be of importance clinically in improving the safety of pulmonary artery banding procedures.

Decreased auxotonic sarcomere shortening in hypertrophied rabbit myocardium.

Auxotonic sarcomere length change occurs during isometric twitches of isolated cardiac muscle preparations. To assess the amount of internal work in hypertrophied myocardium, we measured auxotonic sarcomere length change during isometric tension development over a range of initial muscle and sarcomere lengths. Hypertrophy was produced by banding the pulmonary artery, which resulted in an increase in the ratio of right ventricular free wall weight to total ventricular weight (normal 0.19 +/- 0.004; hypertrophy 0.35 +/- 0.008; P less than 0.001). Right ventricular free wall trabeculae and papillary muscles were studied with optical and mechanical instrumentation, including a helium-neon laser, to measure sarcomere length and isometric twitch parameters. The resting sarcomere length-resting tension relationship was shifted to the left of normal in the hypertrophied preparations (P less than 0.001). The relationship of sarcomere length at the peak of the twitch with total tension at the same instant was shifted downward and to the right of normal in hypertrophy (P less than 0.01). For the same amount of total tension development there was less than normal sarcomere shortening in the hypertrophied preparations (P less than 0.001). Consequently, there is less than normal work per sarcomere during auxotonic sarcomere shortening in hypertrophied heart muscle. Less sarcomere work for a particular functional state is important to consider in the assessment of the basis of myocardial function in compensated pressure overload hypertrophy.

Coronary Vasodilator Reserve in Young Dogs with Moderate Right Ventricular Hypertrophy

The effects of experimental right ventricular (RV) pressure overload and RV hypertrophy on coronary vasodilator reserve in young animals is not well established. Therefore, we measured coronary vasodilator reserve in the right ventricle of dogs from 7 to 12 months old with moderate RV hypertrophy due to pulmonary artery banding performed 3 to 7 days after birth. In the 5 dogs with pulmonary artery banding, substantial RV hypertension developed (RV pressure at rest, 73 ± 11 mm Hg) as did RV hypertrophy (ratio of RV free wall/left ventricular free wall weight, 1.86 ± 0.41 gm/kg). The reactive hyperemic response following brief coronary occlusions was used as an index of coronary vasodilator reserve. The ratios of peak reactive hyperemic response to resting flow, however, were not significantly different in the 5 banded dogs compared with 7 control animals (3.6 ± 1.0 versus 2.6 ± 0.6); this implies that the extent of vasodilator reserve was similar with or without moderate RV hypertrophy. In addition, myocardial blood flow, as determined using radioactive microspheres, was not significantly different at rest: 0.57 ± 0.09 ml/min per gram in the banded dogs versus 0.48 ± 0.12 ml/min per gram in the controls. Uniform transmural distribution of blood flow was maintained during infusion of isoproterenol, which was used to increase myocardial oxygen requirements in both groups. Minimum coronary vascular resistance was significantly lower in the banded than the control dogs (1.5 ± 0.6 versus 6.2 ± 2.3; p < 0.01). This difference suggests that the cross-sectional area of the right coronary vascular bed increased with the development of RV hypertrophy.

Quantitative assessment of growth and function of the cardiac chambers in the normal human fetus: a prospective longitudinal echocardiographic study.

We assessed the changes in cardiac chamber size, architecture and function in the normal fetus in a prospective, longitudinal, two-dimensional, and two-dimensionally directed M mode echocardiographic study. Serial echocardiograms were recorded in 16 normal fetuses at 4 week intervals from 20 weeks gestation to parturition. Fetal gestational age was assessed by biparietal diameter. Left ventricular, right ventricular, and left atrial chamber sizes and aortic diameter all increased linearly with age. The ratios of right and left ventricular diameter, left atrial to aortic diameters, and relative left ventricular wall thickness that we used as an index of short-axis left ventricular architecture remained constant. Fractional right ventricular and left ventricular wall thicknesses were similar both on echocardiograms and in postmortem hearts over the same range of gestational ages. In addition, postmortem right ventricular and left ventricular free wall weights were indistinguishable and contributed the same proportion to total heart weight throughout gestation. Left ventricular echocardiographic mass increased linearly from a mean of 0.86 +/- 0.09 to 7.47 +/- 2.43 g at term and corresponded closely with postmortem left ventricular weight. We conclude that (1) fetal cardiac chamber dimensions, wall thicknesses, and left ventricular mass increased with gestational age, (2) cardiac architecture in terms of the ratios of right ventricular/left ventricular diameters, left atrial/aortic diameters, and relative wall thickness remained constant, (3) right and left ventricular fractional shortening did not change with age, (4) left ventricular mass assessed echocardiographically corresponded closely with postmortem left ventricular weights in fetal hearts of similar gestational ages, and (5) the similarities between right and left ventricular sizes, wall thicknesses, and free wall weights in this study do not support the theory of right ventricular dominance in the human fetus.

Polyamine metabolism during the perinatal development of the rabbit right and left ventricle.

The right ventricular (RV) and left ventricular (LV) free wall weights, ornithine decarboxylase (ODC) specific activity and polyamine content were determined in fetal, 1-, 2-, 7-, 14-, and 21-day-old rabbit hearts. There was a significant increase in the LV free wall weight and a decrease in RV free wall weight between 1-7 days. By day 7 the LV/RV mass ratio doubled and reached a ratio comparable to that seen in adult rabbit hearts. The rate of change in the LV and RV free wall weights were comparable after day 7. There was a significant increase in LV ODC specific activity and a decrease in RV ODC specific activity after birth. The LV ODC specific activity was significantly greater than RV ODC specific activity in both 1 and 2 day old rabbit hearts whereas they were not significantly different in 7 and 14 day old rabbit hearts. The molar content (nmoles/mg wet weight or nmoles/mg protein) of putrescine decreased approximately 3-fold after birth in the RV but increased approximately 2-fold in the LV. The molar content of spermidine and spermine was transiently increased after birth (1 day old) in both RV and LV with approximately a 2-fold increase in spermidine and a 2.5-fold (LV) and 4-fold (RV) increase in spermine content. The increase in LV putrescine content after birth was due, at least in part, to the observed increase in ODC specific activity in the LV free wall. The putrescine/spermidine ratio increased in the LV and decreased in the RV immediately after birth up to day 7. As opposed to the short-lived increase in spermidine and spermine observed in both the RV and the LV free wall, increased ODC specific activity and putrescine accumulation uniquely characterized the preferential growth of the LV between day 1 and 7.

Mechanism of physiologic versus pathologic ventricular hypertrophy process: enhanced or depressed myosin ATPase activity and contractility governed by type, degree and duration of inciting stress.

Types of hypertrophy, such as the normal development of the left ventricle of new-born lambs, induction of hypertrophy following administration of subhypertensive doses of norepinephrine, and hypertrophy where moderate pulmonic stenosis is the inciting stimulus, are all of a physiologic nature, i.e., cardiac function is elevated and K+ stimulated myosin ATPase activity is increased. The K+/EDTA stimulated myosin ATPase activity, used as an index of physiologic versus pathologic hypertrophy, may reflect alterations in myosin heavy chains since a large amount of light chains are in the dissociated state with this kinetic system. In experimental conditions where light-chain deficient-myosin was employed there was no corresponding decrease in myosin ATPase activity with the dissociation of light chains, irrespective of the cation activator utilized; there was however a decrease in the enzymatic activity of actomyosin with the loss of light chains. Furthermore, this decrease in actomyosin ATPase activity was partially restored with the reassociation of light chains with light-chain-deficient-myosin. Where excessive hypertrophy occurred, e.g., with moderate pulmonic stenosis, where the right ventricular free wall weight increased 100%, there was a decrease in cAMP content. This may result from the subsequent decrease in stress per sarcomere following massive hypertrophy. Where there was a lesser degree of hypertrophy, e.g., with mild pulmonic stenosis, creating a transitory 30% increase in right ventricular free wall weight, there was no subsequent decrease in cAMP content.

Phosphorylative respiratory activity of mitochondria isolated from the left and right ventricles of rabbit hearts following partial pulmonary trunk occlusion

Right ventricular hypertrophy was produced by placing a spiral Monel metal clip around the pulmonary trunks of rabbits causing a sustained 67% occlusion of the vessel. The operation produced a doubling of right ventricular weight, by 13 days post-surgery, which persisted throughout the post-operative period studied (13 to 84 days); only a slight increase in left ventricular free wall weight was observed. Isolated mitochondria exhibited region-specific changes with time in state 3 Q o 2. Thirteen days after operation, the state 3 Q o 2 of right ventricular mitochondria was depressed to about 85% of controls. Thereafter, respiration increased fairly sharply, peaking at just above control values by 40 days post-operation. Finally, it declined abruptly to about 70% of controls by 84 days. A very different pattern of change was observed when left ventricular mitochondrial respiratory activities were examined. Thirteen days after the operation, state 3 Q o 2 was elevated somewhat above controls. Thereafter, it declined linearly and gradually, dropping to about 85% of controls by 84 days.

Changes in cAMP concentrations during chronic cardiac hypertrophy

Mild pulmonic stenosis in the dog, where right ventricular peak systolic pressure was increased approximately 150% at the time of sacrifice, induced 100% or more increase in right ventricular free wall weight by 3 weeks postoperative. Accompanying cardiac hypertrophy at these postoperative times, there was a decrease in both tissue PO2 levels and cAMP concentrations in the hemodynamically stressed ventricle, the right ventricle. Myosin ATPase activity was elevated as well as the velocity of contractile element shortening. The hemodynamically nonstressed left ventricle did not hypertrophy at these early postoperative times.