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Biomedical subjects

M V Hart

Publications and source records attributed to M V Hart.

11 recordsLinked to original sources

Exercise induced augmentation of cellular and humoral autoimmunity associated with increased cardiac dilatation in experimental autoimmune myocarditis.

To determine the effects of exercise in experimental autoimmune myocarditis, guinea pigs immunised with heterologous heart protein (rat heart), Freund's complete adjuvant, and pertussis vaccine (treated group) were exercised on a treadmill for a total of 11 weeks and compared with non-exercise treated animals. In vivo heart rates and pressures, in vitro left ventricular pressure-volume relations, myocardial histology, circulating antiheart antibody, and in vitro lymphocyte stimulation were determined. Exercise resulted in increased cardiac dilatation in treated animals as assessed by in vitro left ventricular pressure-volume relations compared with non-exercise treated animals (at 8 mmHg 1.41(0.17) ml.kg-1 vs 1.20(0.17) ml.kg-1 respectively, p less than 0.005). Exercise also resulted in increased concentrations of circulating antiheart antibody as assessed by radioimmunoassay (0.14(0.04) microgram vs 0.10(0.03) microgram respectively, p = 0.01), and increased lymphocyte activation to specific antigen (stimulation index 3.7(0.07) vs 2.4(1.0) respectively, p less than 0.001). Despite the associated augmentation of autoimmunity with cardiac dilatation, there were no differences in the histopathological findings between the exercised treated and the non-exercised treated animals either qualitatively or quantitatively (number of inflammatory cell microaggregates). This finding suggests that, although the immune system is important in experimental autoimmune myocarditis, the amount of inflammation and necrosis does not appear to correlate with the degree of left ventricular dilatation and presumed dysfunction.

Animals

Thermodilution cardiac output determination in the guinea pig.

Thermodilution cardiac output was compared with simultaneously determined aortic flow in 5 guinea pigs during thoracotomy. Total cardiac output was affected by volume expansion, adrenergic stimulation, and the volume of hemorrhage. For the equation y = mx, where y is aortic flow, x is thermodilution cardiac output, and m is the slope of the regression line, m = 0.88 +/- 0.02 (95% confidence interval). The SE of the regression was 27.8 ml/min. Thermodilution may have been overestimated because the aortic flow measurement did not take into account the coronary arterial blood flow, which is approximately 4% of total cardiac output in the guinea pig. Indicator loss (ie, temperature) also may be an important factor in the calculation of cardiac output, as determinations of thermodilution cardiac output were affected by sampling site in the guinea pig. Thermodilution appears to be a useful and reliable means of determining cardiac output in the guinea pig.

Animals

Aortic function during normal human pregnancy.

Arterial rupture and dissection have been observed in both normal and complicated pregnancies. To understand how arterial mechanical properties might change during pregnancy, we measured aortic root diameter by M-mode echocardiography and obtained simultaneous cuff blood pressures during systole and diastole at rest and during isometric exercise. Measurements were obtained in 19 women at the end of normal gestation and again 3 to 6 months post partum. The aorta is larger and more compliant during normal human pregnancy, and these changes may not revert to prepregnant levels post partum. Increased aortic compliance, combined with decreased vascular resistance, may enhance left ventricular performance in normal pregnancy. Conversely, the presumed structural alterations leading to increased compliance may weaken diseased vessels leading to dissection or rupture during pregnancy.

Adolescent

Maternal heart rate and stroke volume in the pygmy goat: effects of exercise and cardiac autonomic blockade.

To determine the normal maternal heart rate and stroke volume response to exercise and the role of the autonomic nervous system in this response, pregnant and non-pregnant pygmy goats were studied at rest, during and following treadmill exercise, and after autonomic blockade. Resting heart rates, stroke volumes and cardiac outputs were 10%, 60%, and 76% higher in pregnant compared to non-pregnant animals (P less than 0.05, 0.001, and 0.001 respectively). During exercise, heart rate and stroke volume rose in both pregnant and non-pregnant animals by similar amounts. Immediately post-exercise, stroke volume in pregnant animals dropped precipitously below resting levels by 15% (P less than 0.005) but cardiac output was preserved by heart rate. This fall in stroke volume was not seen in control animals. Autonomic blockade lowered resting and exercise heart rates in both groups without changing stroke volume. The elevations in heart rate and stroke volume in pregnancy are not primarily mediated via the autonomic nervous system. Although the maternal cardiac output response to exercise appears normal, the post-exercise fall in stroke volume, presumed secondary to a reduction in preload, could potentially be harmful to both mother and fetus.

Animals

Exercise dynamics in late gestation: effects of physical training.

Heart rate and stroke volume were measured serially in subjects at rest in the sitting position and at the onset and end of a 6-minute period of upright bicycle exercise. Twenty-three subjects with normal pregnancy were studied in late gestation and again post partum. Rest and exercise cardiac outputs in late gestation were not different from those in the postpartum period. Heart rate was higher at rest and stroke volume lower during exercise in late gestation than post partum. At the end of exercise, stroke volume fell dramatically in late gestation but not post partum. Ten women prospectively identified as physically fit had responses that were not different from those of the nonfit cohort in late gestation. Post partum, the physically fit women had exercise responses typical of trained persons and different from those of the nonfit cohort. In late gestation, rest and exercise hemodynamics in subjects in the sitting position appeared to be dominated by factors influencing venous return, independent of physical fitness.

Birth Weight

The effect of castration and sex steroids on ventilatory control in male guinea pigs.

Male guinea pigs (N = 7) given progesterone hyperventilate with PaCO2 falling from control levels of 39.0 +/- 0.6 (SEM) Torr to 32.0 +/- 0.7 Torr after 7 days of treatment. This response was associated with a rise in plasma progesterone concentration to approximately 15 ng ml-1 and a transient rise in plasma 17 beta-estradiol concentrations. To determine the role of the testes in generating the transient estrogen increase as well as the significance of estrogens to the progesterone response, male guinea pigs were castrated and treated either with estradiol or a placebo. Estrogen-treated castrates (N = 15) had a mean PaCO2 of 36.1 +/- 0.8 Torr and the castrates given the placebo (N = 7) had an average PaCO2 of 43.8 +/- 1.2 Torr (P less than 0.001). Both of these castrate groups were also different from intact, untreated males (P less than 0.01). Progesterone concentrations were very low and not different. When progesterone was additionally administered, the PaCO2's fell to 33.0 +/- 0.8 and 38.2 +/- 0.6 Torr for the estrogen- and placebo-treated castrate groups, respectively. The male guinea pig hyperventilates when given progesterone with the magnitude and time course of his response comparable to the human's. The response to progesterone is not critically dependent on the testes or on plasma estrogen concentrations; however, both castration and exogenous estrogen appear to influence PaCO2 without altering plasma progesterone concentrations.

Animals

Experimental autoimmune myocarditis in the guinea pig.

Male and female guinea pigs underwent immunisation with heterologous heart protein (rat heart), complete Freund's adjuvant and pertussis vaccine (immunised) or normal saline (control) at weekly intervals for 6 weeks, and were subsequently studied. In vivo intracardiac pressures, cardiac outputs, blood volumes, in vitro pressure-volume relations, left ventricular collagen contents, light microscopy, direct immunofluorescence, lymphocyte stimulation studies, and serology for circulating anti heart antibody (haemagglutination and radioimmunoassay) were performed. Immunised guinea pigs studied between 5 and 8 weeks following the immunisation protocol demonstrated a 44% increase in LVEDP (p less than 0.005), an increase in right atrial pressure (p less than 0.001), although no change in aortic pressure or cardiac output when compared with controls. Left ventricular weight was increased 20% (p less than 0.001), and in vitro left ventricular volume by 34% (at 8 mmHg distending pressure, p less than 0.001). Lung wet weight was increased 44% (p less than 0.005), and left ventricular collagen content increased 60% (p less than 0.001). Cultured lymphocytes from treated guinea pigs demonstrated a 1.5- to 4.5-fold (dependent upon proximity to last immunisation) increase in radiolabelled thymidine uptake when incubated with guinea pig heart protein compared to controls (p less than 0.001), and circulating anti guinea pig heart antibodies were detected by haemagglutination and radioimmunoassay. Histological examination of the left ventricles revealed inflammatory cell infiltration and myocyte increase to varying degrees in 15 of the 18 treated animals. We conclude that inflammatory, probably immune-mediated, chronic myocarditis can be produced in the guinea pig.

Animals

Hemodynamics during pregnancy and sex steroid administration in guinea pigs.

We investigated the time course and possible mechanisms by which the maternal cardiovascular system adapts to the demands of pregnancy. Control, 20-, 40-, and 60-day gestation guinea pigs (total 68 days) and nonpregnant virgin female guinea pigs chronically dosed with cholesterol (control), estrogen (17beta-estradiol), progesterone, and estrogen plus progesterone were studied. In vivo heart rates, pressures, cardiac outputs, blood volumes, and in vitro left ventricular pressure-volume relations were measured. There was no difference in heart rate, mean arterial, right atrial, or left ventricular end-diastolic pressures, or left ventricular weights between the various pregnant animals or hormone-dosed animals and their respective controls. By 20 days gestation blood volume (24%, P less than 0.005), cardiac output (22%, P less than 0.005), and stroke volume (22%, P less than 0.05) were increased, whereas uterine blood flow was unchanged. Chronic estrogen administration resulted in similar increases in cardiac output (24%, P less than 0.05), stroke volume (31%, P less than 0.05), and blood volume (13%, P less than 0.05). In vitro left ventricular pressure-volume relations were shifted to the right in all pregnant and hormone-dosed groups. Increases in left ventricular size and output occur before changes in uterine blood flow in guinea pig pregnancy, and these adaptations can be elicited by chronic sex steroid administration.

Animals

Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus.

Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment, major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.

Adolescent

Hemodynamics in the guinea pig after anesthetization with ketamine/xylazine.

The resting hemodynamics were determined in 8 guinea pigs after they were anesthetized with ketamine/xylazine. Measurements were made of blood pressure, heart rate, cardiac output, arterial blood gases, and pH. These measurements were obtained initially at 4 to 5 hours after an injection (IM) of ketamine HCl (25 mg) and xylazine (0.15 mg) was given to anesthetize the animals for catheterization (period 1), again 5 days after the operation (period 2), and finally 4 to 5 hours after a 2nd injection of ketamine/xylazine (period 3). There were no differences in heart rates, respiratory rates, or cardiac outputs among the 3 study periods. However, arterial blood pressure was slightly, but significantly, lowered after, and presumably due to, instrumentation (62 +/- 4 mm of Hg, P less than 0.05) when compared with the 5-day postoperative period (67 +/- 7 mm of Hg) or after the readministration of anesthetics (66 +/- 7 mm of Hg). The partial pressure of carbon dioxide in the arterial blood was slightly lower (4 mm of Hg, P less than 0.05) in both acutely postanesthetic periods (period 1 and period 3) than in the same animals at postoperative day 5 (period 2). This study has demonstrated that resting hemodynamics measured shortly after this anesthesia with ketamine/xylazine are not largely different from those in chronically instrumented animals.

Anesthesia, General

Progesterone-induced hyperventilation in the guinea pig.

Progesterone-induced hyperventilation has thus far not been reported in animals other than humans. Accordingly we investigated the effects of chronic progesterone treatment on ventilation in guinea pigs. Virgin female guinea pigs were divided into those treated with cholesterol as controls (C), progesterone (P), or estrogen plus progesterone (E&P). All hormones were administered in silastic capsules placed subcutaneously for 28 days. On day 28 arterial blood gases and respiratory rates were determined. Arterial pH was elevated in P- and E&P-treated animals compared with controls (7.43 +/- 0.04 and 7.43 +/- 0.03 vs 7.39 +/- 0.05, respectively, P less than 0.05). Arterial PCO2 was reduced in both progesterone-treated groups compared to controls (33.9 +/- 5.8 (P), 33.1 +/- 2.8 (E&P), 38.0 +/- 4.3 (C)), and was correlated with systemic progesterone concentrations in animals receiving E&P (r = -0.85, P less than 0.01) but not in animals receiving P alone (r = -0.07, P = N.S.). Arterial [HCO-3], PO2 and respiratory rates were not different between groups. We conclude that chronic progesterone administration produces hyperventilation in guinea pigs, and that estrogen facilitates this action of progesterone.

Animal Diseases