Neonatal Pig Hearts Research Articles

Metabolic and Mechanical Responses to Right vs. Left Ventricular Volume Loading in the Neonatal Pig Heart. • 114

Metabolic and Mechanical Responses to Right vs. Left Ventricular Volume Loading in the Neonatal Pig Heart. • 114

Contractile and coronary vascular effects of pituitary adenylate cyclase activating polypeptide in neonatal pig hearts

Contractile and coronary vascular effects of pituitary adenylate cyclase activating polypeptide in neonatal pig hearts

Contractile and coronary vascular effects of pituitary adenylate cyclase activating polypeptide in neonatal pig hearts

The purpose was to investigate the influence of the 38-amino-acid neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP38), on contractile function and coronary vascular tone in neonatal hearts. Isolated, paced (150 bpm), isovolumically-beating, piglet hearts (n = 19) underwent retrograde aortic perfusion at constant coronary flow (approximately 2.5 ml/min/gwet) with an erythrocyte-enriched (Hct 15-20%) solution (37 degrees C). Agonists were injected into the aortic root of hearts, and the changes in +dP/dtmax and -dP/dtmax (reflecting contractility), and coronary perfusion pressure (reflecting vascular tone) were determined. Responses to PAPCAP38 were compared to isoproterenol, and to the truncated peptide PACAP6-38. PACAP38 (0.1 and 0.5 nmol) increased +dP/dtmax from 1387.4 +/- 134.6 to 1619.0 +/- 118.7, and from 1296.2 +/- 93.4 to 1872.2 +/- 111.4 mmHg/s (P < 0.05); changed -dP/dtmax from -1087.6 +/- 107.5 to -1206.6 +/- 93.6, and from -1025.0 +/- 46.8 to -1375.4 +/- 80.9 mmHg/s (P < 0.05) and decreased coronary perfusion pressure from 61.8 +/- 2.5 to 51.0 +/- 3.8, and from 62.5 +/- 1.0 to 45.3 +/- 3.3 mmHg (P < 0.005), respectively. In comparison, isoproterenol (0.1 nmol) increased +dP/dtmax from 1313.6 +/- 62.8 to 1679.0 +/- 74.4 (P < 0.05), and -dP/dtmax from -1026.4 +/- 54.1 to -1222.6 +/- 57.4 mmHg/s (P < 0.05). PACAP6-38 reduced PACAP38's coronary vasodilatory, but not its contractile, effect. When compared to our previous studies of the 27-amino-acid neuropeptide PACAP27, PACAP38 had less potent contractile, but similar vasodilatory effects. PACAP38 enhanced contractility and produced coronary vasodilation in piglet hearts, which may make PACAP38 a promising cardiotonic agent for the treatment of neonates with heart failure.

Vascular and contractile function and tissue metabolites after prolonged hypothermic ischaemia and reperfusion: Comparison of single- versus multi-dose infusions with two cardioplegic solutions in blood-perfused neonatal pig hearts

The effects of single- and multi-dose cardioplegia on post-ischaemic vascular function and contractile activity were compared in 69 blood-perfused neonatal pig hearts, as were the protective properties of two different cardioplegic solutions. Hearts ( n = 6 or 9 per group) from neonatal (3–5 days old) pigs were excised, arrested with a 2 min infusion (at 15°C) of St Thomas' Hospital cardioplegic solution number 1 (STH1) or number 2 (STH2), and then maintained in a state of hypothermic (15°C) ischaemia for 6 or 8 h. Hearts in the multi-dose groups received cardioplegia every hour (2 min at 15°C). At the end of ischaemia all hearts were reperfused (60 ± 2 mmHg perfusion pressure) for 40 min with blood from a support pig. Systolic and diastolic functions were assessed with an intraventricular balloon, and endothelial and smooth muscle functions by measuring the response to infusions of defined concentrations of acetylcholine (8, 16 and 32 μg/min) and glyceryl trinitrate (40, 80 and 160 μg/min). Hearts ( n = 9) not subjected to ischaemia were perfused for the same duration to act as aerobic controls. At the end of the perfusion period, hearts were frozen and taken for metabolite analysis. After 8 h ischaemia, the recovery of left ventricular developed pressure was greatest in the multi-dose STH1 and single-dose STH2 groups (113 ± 6 and 117 ± 6 mmHg, respectively, v 128 ± 9 mmHg in aerobic controls, at an end-diastolic pressure of between 3 and 9 mmHg; P = N.S.) and the poorest in the single-dose STH1 group (92 ± 5 mmHg; P < 0.05 v controls). The recovery of diastolic function was greatest in the multi-dose STH2 group and again poorest in the single-dose STH1 group (left ventricular enddiastolic pressure 1 ± 2 and 30 ± 10 mmHg, at a ventricular volume of 3.0 ml, ν-1 ± 1 mmHg in aerobic controls). Vascular responses to acetylcholine and glyceryl trinitrate and the myocardial high-energy phosphates content were better preserved in multi-dose groups and with STH2. Inter-group differences were less when the duration of ischaemia was reduced to 6 h. In conclusion, the neonatal pig heart was best preserved with multi-dose cardioplegia and STH2 was more efficacious than STH1. However, not all indices were optimally protected by multi-dose STH2. Thus the best protection of systolic function was obtained with multidose STH1and this was followed by single dose STH2. Diastolic was best preserved with multi-dose STH2 as were vascular function and high-energy phosphates.

Mechanical and metabolic characterization of ischemic contracture in the neonatal pig heart.

Isolated, paced, isovolumetrically beating piglet hearts (n = 37) underwent retrograde aortic perfusion with a crystalloid solution during three periods: 1) baseline (coronary perfusion pressure 60 mm Hg), 2) ischemia (coronary flow 10% of baseline for approximately 80 min), and 3) reperfusion (perfusion pressure returned to baseline). In one group of hearts, glycolysis (using 3H2O formation from [3H]glucose) was assessed. During baseline, peak systolic pressure (PSP) was 101.1 +/- 5.0 mm Hg, end diastolic pressure (EDP) 4.4 +/- 0.5 mm Hg, glycolysis 970.5 +/- 65.3 nmol/min/gwet, and myocardial glycogen 234.8 +/- 12.0 mumol/gdry. During ischemia, PSP decreased to 23.3 +/- 2.7 mm Hg, EDP increased to 12.3 +/- 0.7 mm Hg, myocardial glycogen decreased to 181.5 +/- 30.3 mumol/gdry, and lactate (approximately 154 mumol/gwet) and glycerol (approximately 930 nmol/gwet) were released. Myocardial contracture correlated with a decrease in lactate release. Glycolysis decreased to approximately 400 nmol/min/gwet and remained stable, accounting for approximately 50% of the lactate produced. During reperfusion, PSP recovered to 79.8 +/- 3.5 mm Hg, EDP 6.6 +/- 1.7 mm Hg, and glycolysis 1103.9 +/- 81 nmol/min/gwet. In a second group of hearts, with similar mechanical responses, glucose oxidation (using 14CO2 formation from [14C]glucose) was evaluated. During baseline, glucose oxidation was 165.4 +/- 15.9 nmol/min/gwet and correlated closely (r = 0.957) with mechanical activity. With ischemia, glucose oxidation decreased to approximately 17 nmol/min/gwet, yet accounted for approximately 42% of the ATP produced. Upon reperfusion, glucose oxidation returned to baseline values, but now correlated poorly (r = 0.574) with mechanical activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of rapid growth in the neonatal pig heart

During the first 2 weeks of life the left ventricular free wall of the neonatal pig heart grows rapidly. The mass of the left ventricular free wall (LVFW) increased from 2.22 +/- 0.10 g to 9.62 +/- 1.01 g while the right ventricular free wall (RVFW) increased from 2.03 +/- 0.24 g to 3.56 +/- 0.41 g from birth to 14 days of age. During the same period, the cellular volume of myocytes from the LVFW increased from 1075 microns3 to 3688 microns3 while myocytes from the RVFW increased in volume from 1511 microns3 to 2454 microns3. The number of RVFW myocytes did not change during the first 2 weeks of life, while the number of LVFW myocytes increased 28%. Myocytes from both ventricles were approximately 90% mononuclear from birth to 4-5 days of age. By 14 days, 67% of LVFW myocytes and 53% of RVFW myocytes were multinucleated. When growth of the heart was restrained by treatment of the piglet with enalapril maleate, the LVFW mass was reduced by 24% over 2 weeks compared to hearts from untreated piglets and was accounted for by a reduction in myocyte volume. Enalapril treatment did not alter the number of myocytes in either the LVFW or RVFW as compared to hearts from untreated piglets. After 14 days of enalapril treatment, the percentage of multinucleated cells was reduced in the LVFW and unchanged in the RVFW as compared to hearts from untreated piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasoconstriction mediated by endothelin-1 in neonates: Reversal by nitroglycerin

To determine the role of the vasoconstrictor peptide endothelin-1 in cardiopulmonary bypass in neonates, we measured plasma endothelin-1 concentrations in infants before and after cardiopulmonary bypass for arterial switch procedures and studied the effects of endothelin-1 on coronary tone and contractility in normal and reperfused neonatal pig hearts. Endothelin-1 blood concentrations (picograms per milliliter, mean ± standard error) were significantly higher in neonates with arterial transposition and in umbilical venous blood (22.9 ± 2.3 and 19.2 ± 2.9, respectively) than in older children with atrial septal defects (13.2 ± 1.6) or in healthy adults (10.7 ± 2.5). After cardiopulmonary bypass, endothelin-1 concentrations increased 29% in neonates undergoing arterial switch procedure and 28% in children undergoing atrial septal defect repair ( p < 0.05 versus before bypass). In isolated, blood-perfused neonatal pig hearts, endothelin-1 had dose-related coronary constrictor and inotropic effects between 25 and 100 pmol. Endothelin-1 concentrations that did not increase coronary perfusion pressure (5 to 10 pmol) caused significant coronary constriction in the presence of norepinephrine (10 nmol/L). During reperfusion after 30 minutes of global normothermic ischemia, the coronary vasoconstrictor effects of both endothelin-1 alone and endothelin-1 plus norepinephrine were significantly enhanced. Nitroglycerin reversed vasoconstriction produced by endothelin-1 and endothelin-1 plus norepinephrine both before and after ischemia-reperfusion. We conclude that endothelin-1 concentrations are significantly elevated in neonates and are further increased after cardiopulmonary bypass. Coronary vasoconstriction caused by endothelin-1 is enhanced by ischemia-reperfusion and by norepinephrine present in concentrations typically observed after neonatal cardiopulmonary bypass. Nitroglycerin reverses coronary vasoconstriction induced by endothelin-1 and may therefore be beneficial in the postoperative management of neonates after cardiac operations. (J T horac C ardiovasc S urg 1995; 109:88-98)

Endothelium-Dependent Regulation of Coronary Tone in the Neonatal Pig

We examined the effects of endothelium-dependent responses on coronary perfusion pressure (CPP) in isolated, blood-perfused neonatal pig hearts under conditions of controlled coronary flow. Baseline CPP was increased 8%-21% by the cyclooxygenase inhibitor indomethacin (10-100 microM), and 30%-92% by NG-monomethyl-L-arginine (L-NMMA, 10-100 microM), an inhibitor of nitric oxide (NO) synthase, suggesting that both prostaglandin and nitric oxide synthesis contribute to basal coronary tone. Both acetylcholine (ACh) and bradykinin (BK) decreased CPP. These effects were enhanced by preconstriction with endothelin-1. L-NMMA markedly attenuated BK-induced coronary vasodilation and converted the ACh response to constriction, indicating a significant role for NO release in these responses. After 1 h of total, global normothermic ischemia and 45 min of reperfusion, vasoconstrictor responses to endothelin-1 and ACh were enhanced, while BK-induced dilation was significantly reduced. L-Arginine supplementation during reperfusion did not restore vasodilatory responses to ACh or BK. The magnitude of L-NMMA-induced coronary vasoconstriction during reperfusion was similar to that observed without ischemia-reperfusion. Coronary vasodilation in response to sodium nitroprusside, a NO precursor that causes endothelium-independent vasodilation by directly activating smooth muscle guanylate cyclase, was unaffected by ischemia-reperfusion. We conclude that NO production in the neonatal coronary circulation contributes to both basal tone and the response to ACh and BK. After ischemia-reperfusion, basal NO production and smooth muscle relaxation mediated by guanylate cyclase are intact, whereas agonist-stimulated dilation is significantly impaired.

Insulin Reduces Basal Release of Atrial Natriuretic Factor by Isolated, Perfused Neonatal Pig Hearts

Plasma atrial natriuretic factor (ANF) levels are markedly altered in diabetic rodents suggesting that insulin might be a modulator of ANF release. Effects of insulin (25 mU/ml) on basal (nonstimulated) immunoreactive (ir)-ANF release by isolated neonatal pig hearts paced at 150 beats/min and perfused with no change in atrial stretch were examined. Release of ir-ANF decreased with age from 1-3 days postpartum (146.0 +/- 38.4 to 62.2 +/- 20.5 fmol/g/min). Insulin stimulated myocardial glucose utilization and lactate production approximately 2-fold, but uniformly decreased ir-ANF release by approximately 25%, regardless of age. Correlations between ir-ANF release and myocardial metabolism suggest independent influences of insulin on these two events. In addition, it appears that this model might be reasonably exploited to investigate episodic ANF release and its regulation during ontogeny and in a variety of physiological states.

Control of growth in neonatal pig hearts.

The pig heart grows at a maximal rate in the first 2-3 days of life due to a volume overload imposed on the heart at birth. Rates of ribosome formation and protein synthesis cannot be further accelerated during in vitro perfusion with agents that increase cyclic AMP, that bind to alpha 1-adrenergic receptors or that bind to angiotensin II receptors. Growth of the heart in vivo can be restrained by treatment with an angiotensin-converting enzyme inhibitor, enalapril maleate, or an angiotensin receptor antagonist, DuP 753. In the enalapril-treated heart, norepinephrine plus propranolol, but not angiotensin II, accelerated ribosome formation. Rapid growth of the left ventricle of pig heart during the first 10 days of life is due largely to eccentric hypertrophy.

Detection of angiotensin I and II in cultured rat cardiac myocytes and fibroblasts.

Angiotensin II (ANG II) is a stimulus for positive chronotropic and inotropic effects, protein synthesis, and hypertrophic growth in cardiac tissue. These short- and long-term effects of ANG II are mediated through specific plasma membrane receptors. Indirect evidence suggests that ANG II synthesized in the myocardium may be important in regulating cardiac function. The cell types in the myocardium that produce components of the renin-angiotensin system have not been determined. In this study, we evaluated whether cultured cardiomyocytes and fibroblasts obtained from ventricles of neonatal rat hearts were capable of synthesizing ANG I and II. Both cardiomyocytes and fibroblasts were found to have immunofluorescent staining for ANG I, ANG II, and angiotensin-converting enzyme (ACE). The amounts of ANG I and II in cell extracts and conditioned media obtained from cardiomyocytes and fibroblasts were quantified by radioimmunoassay. The amounts of ANG I and II detected in cardiomyocyte cultures (1.48 x 10(6) cells/dish) were 32.2 +/- 16.2 (n = 4) and 6.2 +/- 2.9 (n = 4) ng/10(6) cells, respectively. The amounts of ANG I and II detected in the media conditioned by a 48-h exposure to cardiomyocytes were 5.2 +/- 1.2 (n = 3) and 2.1 +/- 1.2 (n = 3) ng/10(6) cells, respectively. The amounts of ANG I and II detected in fibroblast cultures (5.38 x 10(6) cells/dish) were 34.8 +/- 4.9 (n = 4) and 8.0 +/- 3.5 (n = 4) ng/10(6) cells, respectively. The amounts of ANG I and II obtained from media conditioned by a 48-h exposure to fibroblasts were 4.7 +/- 0.6 (n = 4) and 3.3 +/- 2.1 (n = 4) ng/10(6) cells, respectively. The identity of the radioimmunoassayable materials as ANG I and II peptides was confirmed in cardiomyocytes using an in vitro bioassay based on displacement of 125I-ANG II from receptor binding sites in cardiac membranes prepared from neonatal pig heart. Identification of ANG I and II and ACE in vitro in cultures of cardiac myocytes and fibroblasts supports the hypothesis that there is an intracardiac renin-angiotensin system that produces these peptides.

Acetylcholine-induced coronary vasoconstriction and negative inotropy in the neonatal pig heart.

We investigated the influence of exogenously administered acetylcholine, nitric oxide, ADP, ATP, bradykinin, and substance P on coronary vascular tone in isolated, neonatal pig hearts (less than or equal to 4 d). Paced (180 bpm), isovolumically beating hearts underwent retrograde aortic perfusion, with an erythrocyte-enriched solution (hematocrit 0.15-0.20) at constant coronary flow (approximately 2.5 mL/min/g) corresponding to a perfusion pressure of approximately 60 mm Hg. Agonists were injected into the aortic root, and the peak change in coronary perfusion pressure from baseline and left ventricular pressure development were assessed. Nitric oxide (3 microL), ADP (30 nmol), ATP (30 nmol), bradykinin (125 ng), and substance P (50 ng) decreased the perfusion pressure (vasodilation) by 16.9 +/- 1.2, 25.3 +/- 4.4, 18.3 +/- 1.2, 18.9 +/- 1.4, and 7.1 +/- 1.6 mm Hg, respectively. Acetylcholine (0.5 and 1.0 nmol) produced a modest decrease in perfusion pressure (vasodilatation) of 4.2 +/- 0.8 and 3.8 +/- 0.5 mm Hg, respectively, whereas acetylcholine (5, 20, and 100 nmol) increased the perfusion pressure (vasoconstriction) by 16.7 +/- 2.7, 48.2 +/- 8.2, and 85.3 +/- 15.1 mm Hg, respectively. Acetylcholine also decreased left ventricular peak systolic pressure from 108.7 +/- 5.0 to 69.2 +/- 4.6, 56.3 +/- 6.1, and 48.2 +/- 6.4 mm Hg, for the 5, 20, and 100 nmol doses, respectively. Responses to acetylcholine were abolished by atropine (50 nmol). In a separate group of hearts, indomethacin (10(-6) M) reduced the peak change in perfusion pressure for the 5, 20, and 100 nmol doses of acetylcholine by 87%, 66%, and 48%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxidative metabolism and mechanical function in reperfused neonatal pig heart

Oxidative metabolism in reperfused neonatal myocardium has not been characterized. A blood-perfused isovolumic heart preparation was used to quantify metabolic and mechanical responses of the neonatal left ventricle to global normothermic ischemia and reperfusion. Hearts from piglets aged 2–7 days were subjected to either 2 hrs of total ischemia at 37°C followed by 1 hr of reperfusion or 3 hrs of perfusion alone; glucose and palmitate oxidation were measured in separate experiments by incorporation of the appropriate [ 14C]-labeled substrate into the perfusate. In the pre-ischemic period, glucose, palmitate, and lactate contributed 10%, 41%, and 36%, respectively, to oxidative metabolism. After 2 hrs of total normothermic ischemia, oxidation of exogenous glucose was 165% and 229% of control values at 30 and 60 minutes of reperfusion, respectively; palmitate oxidation was 110% and 143% of control values at these times. Despite increased glucose oxidation, palmitate oxidation accounted for 69% of myocardial oxygen consumption after 1 hr of reperfusion, with glucose responsible for 25%. Lactate use was minimal during reperfusion. Reperfusion was accompanied by rapid and parallel recovery of oxygen utilization, mechanical function, and high-energy phosphates. The neonatal piglet heart demonstrates significant metabolic and mechanical tolerance to prolonged ischemia. Although glucose utilization increased markedly, palmitate was the primary substrate for energy production in the post-ischemic neonatal heart.

Myocardial protection of neonatal heart by cardioplegic solution with recombinant human superoxide dismutase

The effectiveness of high-potassium cardioplegic solution in the neonatal heart remains controversial. Our previous study indicated that the protection afforded by a cardioplegic solution was inadequate in the neonatal heart. On the hypothesis that oxyradicals were responsible for the ineffectiveness of cardioplegic solution in neonatal heart, the effects of a cardioplegic solution (a modified St. Thomas' Hospital cardioplegic solution) with recombinant human superoxide dismutase on the isolated perfused neonatal guinea pig hearts (within 2 days after delivery, body weight of 60 to 120 g) were studied in comparison with those on the adult hearts (6 to 8 weeks after delivery, body weight of 300 to 500 g). After arrest induced by modified St. Thomas' Hospital cardioplegic solution, hearts were subjected to 120 min of ischemia at 20 °C, during which time the cardioplegic solution was injected every 30 minutes. Then the heart was reperfused for 60 minutes at 37 °C. Under this condition, the left ventricular developed pressure recovered to 84.4% ± 4.0% of the preischemic value in the adult heart, whereas the recovery was only 68.1% ± 3.1% in the neonatal heart. Thiobarbituric acid-reactive substance level, a parameter of lipid peroxidation by oxyradicals, significantly increased during ischemic arrest both in the adult and neonatal heart. However, the increase was much greater in the neonatal heart than in the adult. Cardioplegia with recombinant human superoxide dismutase (300 and 1,000 U/mL) significantly inhibited this accumulation of thiobarbituric acid-reactive substance in the neonatal heart; at 1,000 U/mL, the myocardial function of the reperfused neonatal heart recovered to the level of the adult heart. As the activity of endogenous superoxide dismutase was significantly lower in the neonatal heart than in the adult, the beneficial effects of recombinant human superoxide dismutase observed in the neonatal heart were supposed to have resulted from supplementation of deficient antioxidant enzymes.

The effects of milrinone in the neonatal pig heart

Milrinone, a selective inhibitor of phosphodiesterase (PDE), was examined in neonatal hearts and in ventricular myocytes. Isolated, paced (180 beats/min), isovolumically beating hearts from pigs, less than 3 days of age, were perfused with an erythrocyte-enriched solution. In one group (control, n = 6), milrinone was studied at perfusate concentrations of 1, 10, and 100 micrograms/ml. In a second group (postischemia, n = 10), hearts were subjected to 30 minutes of no-flow ischemic arrest, prior to the addition of milrinone. Left ventricular peak systolic pressure (PSP) and end-diastolic pressure, coronary flow (CF), heart rate (HR), and myocardial oxygen consumption (MVO2) were measured. The PSP averaged approximately 100 mmHg during the baseline periods for both groups and decreased to approximately 85 mmHg in those hearts subjected to ischemic arrest. In both groups, PSP increased approximately 14% at the 1 micrograms/ml concentration of milrinone. No additional increases in PSP were observed in the control group at the higher concentrations. However, PSP increased 28% and 41% (p less than 0.05), in the postischemia group at the 10 and 100 micrograms/ml concentrations, respectively. The CF averaged approximately 3 ml/min/g during the baseline periods of both groups and increased significantly at each milrinone concentration. The HR in both groups increased to approximately 200 and approximately 250 beats/min at the 10 and 100 micrograms/ml concentrations, respectively. Additionally, milrinone's effects in intact hearts were found to be comparable to those of isobutylmethyl xanthine (IBMX), a nonspecific PDE inhibitor. In isolated myocytes, however, milrinone produced only modest increases in cAMP levels, compared to IBMX.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of growth in the neonatal pig heart

The newborn heart is an excellent model in which to study cardiac growth because the neonatal period is a normal situation in which the left ventricle (LV) grows rapidly and the right ventricle grows slowly. Accelerated LV growth is in response to mechanical, neural, and endocrine changes at birth. Faster growth of the LV is accounted for by greater capacity for protein synthesis, as evidenced by greater RNA content. At 18 h of life, ribosomes are formed in preference to total heart protein, but at 48 h of life, faster rates of both ribosome formation and total protein synthesis are observed. In the LV of hearts from 2-day-old pigs, these rates are insensitive to the addition of glucagon, 1-methyl-3-isobutylxanthine, or a combination of norepinephrine and propranolol. These observations could result because of maximal growth stimulation already present in the LV of the newborn heart. To restrain LV growth in the neonatal period, we treated pigs with enalapril maleate, an angiotensin II-converting enzyme inhibitor. Enalapril blocked growth of the LV as well as the increase in RNA content. When hearts from enalapril-treated pigs were perfused in vitro, rates of protein synthesis and ribosome formation in the LV were lower. These studies suggest that angiotensin II is an important factor accounting for rapid growth of the neonatal heart in response to pressure overload at birth. adenosine 3',5'-cyclic monophosphate; angiotensin II; cardiac hypertrophy; glucagon; norepinephrine; protein synthesis; ribosome formation

Control of growth in the neonatal pig heart

The newborn heart is an excellent model in which to study cardiac growth because the neonatal period is a normal situation in which the left ventricle (LV) grows rapidly and the right ventricle grows slowly. Accelerated LV growth is in response to mechanical, neural, and endocrine changes at birth. Faster growth of the LV is accounted for by greater capacity for protein synthesis, as evidenced by greater RNA content. At 18 h of life, ribosomes are formed in preference to total heart protein, but at 48 h of life, faster rates of both ribosome formation and total protein synthesis are observed. In the LV of hearts from 2-day-old pigs, these rates are insensitive to the addition of glucagon, 1-methyl-3-isobutylxanthine, or a combination of norepinephrine and propranolol. These observations could result because of maximal growth stimulation already present in the LV of the newborn heart. To restrain LV growth in the neonatal period, we treated pigs with enalapril maleate, an angiotensin II-converting enzyme inhibitor. Enalapril blocked growth of the LV as well as the increase in RNA content. When hearts from enalapril-treated pigs were perfused in vitro, rates of protein synthesis and ribosome formation in the LV were lower. These studies suggest that angiotensin II is an important factor accounting for rapid growth of the neonatal heart in response to pressure overload at birth.

Angiotensin II and left ventricular growth in newborn pig heart

The left ventricle of the neonatal pig heart is a model of rapid physiological cardiac growth that is dependent upon accelerated ribosome formation and increased RNA content. The goals of the present study were to investigate the role of angiotensin II in this rapid growth. Hearts from 3 d old control piglets or piglets that were treated with enalapril maleate, an angiotensin converting enzyme inhibitor, or DuP 753, an angiotensin II receptor antagonist, were used for measurements of left ventricular mass, RNA, DNA and protein. Hearts from enalapril-treated pigs also were used for measurements of rates of ribosome formation and total protein synthesis during perfusion as modified Langendorff preparations. Treatment of piglets with enalapril maleate resulted in decreased left ventricle/body wt ratio, RNA content, total RNA and total protein in the left ventricle. These parameters were unaffected in the right ventricle. In vitro perfusion of hearts from enalapril-treated piglets revealed decreased ribosome formation and total protein synthesis in the left ventricle. Piglets treated with DuP 753 had decreased left ventricle/body wt ratio as well as decreased RNA content, total RNA and RNA/DNA ratio in the left ventricle. These results suggest that angiotensin II may be required for rapid growth of neonatal pig hearts.

O-280 - Myocardial cell ion contents and mechanical function after ischemic arrest in neonatal and adult guinea pig hearts.

O-280 - Myocardial cell ion contents and mechanical function after ischemic arrest in neonatal and adult guinea pig hearts.

Effects of recombinant human superoxide dismutase on the ischemia-reperfusion injury in the isolated adult and neonatal guinea pig heart

Effects of recombinant human superoxide dismutase on the ischemia-reperfusion injury in the isolated adult and neonatal guinea pig heart