Bulbar and suprabulbar control of the cardiovascular autonomic effects during arterial hypoxia in the rabbit.
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Biomedical subjects
Publications and source records attributed to S N Hunyor.
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Staged coronary embolization, causing myocardial microinfarctions, has been shown in dogs and sheep to cause chronic ischemic heart failure (HF) that resembles the hemodynamics of the human condition. However, its histopathological basis remains unclear. We examined the hypothesis that the ventricular remodeling seen in such sheep resembles the histopathology of human ischemic cardiomyopathy (ICM). Understanding the pathophysiology of this model will determine its place in the development of treatment strategies for HF. Global left ventricular (LV) damage resulting in HF was induced by staged coronary embolization in 11 sheep. Six others served as controls (normal control, NC). In HF sheep, the heart was harvested 6 months after LV ejection fraction (EF) had stabilized at <35%. Histopathological profiles were compared in biventricular transverse sections at midpapillary level using computed image analysis. LV end-diastolic volume increased in the HF group from 84.9+/-29 to 122.4+/-30.3 ml (n=11, P<.05), but myocytes across the LV wall in noninfarcted zones decreased (435.7+/-38.2 NC; 297.8+/-48.4/unit area HF; n=11, P<.0001) as did myocyte nuclear density (990.5+/-51.5 NC; 677.5+/-121.1/mm(2) HF, n=11, P<.0001). In contrast, LV replacement and interstitial fibrosis increased as did myocyte diameter in noninfarcted zones: 0.1+/-0.1 to 6.2+/-4.5% (P=.0049); 2.0+/-1.0 to 7.6+/-4.9% (P=.0149); and 10.0+/-0.5 to 15.9+/-2.2 microm (P<.0001), respectively. Although LV myocyte nuclear length increased (10.2+/-1.0 NC; 12.2+/-0.9 microm HF, n=11, P=.0006), right ventricular (RV) myocyte nuclear density and length did not alter. In this ovine chronic HF model, LV dilation and interstitial and myocyte remodeling resemble human ICM.
The sustained haemodynamic effects of prazosin (20-30 mg) and metoprolol (400-800 mg) alone and combined (half-dose) were evaluated in five patients with hypertension, left ventricular hypertrophy, and radiological cardiac enlargement. Measurements were made at rest and during isometric handgrip exercise. Blood pressure at rest was equally well controlled on each regimen. The heart rate and cardiac output (thermodilution) were reduced by metoprolol, even when combined with prazosin. Systolic ejection time was prolonged by metoprolol, but there were no changes in left ventricular dimensions at rest. During isometric handgrip the pressure increments were similar on each of the three regimens, although absolute diastolic pressure was lower on combined therapy. The arterial pressure increment on prazosin therapy was predominantly due to a rapid rise in heart rate and cardiac output, whereas with metoprolol and combined therapy the major contribution to the response was by peripheral vasoconstriction. Moreover, with the latter regimens there was a rapid rise in pulmonary artery occluded pressure, which did not occur with prazosin therapy. In conclusion, metoprolol alone, or combined with prazosin, caused significant depression of cardiac function, which was apparent only when the patients were subjected to the haemodynamic stress of isometric exercise.
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1. Echocardiographic haemodynamic and left ventricular parameters were determined in twenty-one normontensives and thirty-six hypertensives during the last trimester of pregnancy. 2. Equivalent blood pressure control was obtained in hypertensives with bet rest only, oxprenolol or methyldopa, but remained above normotensive levels. 3. Cardiac output was elevated in the last trimester of pregnancy in normotensivves and hypertensives. 4. Left ventricular mass was increased in normal pregnancy, but displayed an exaggerated increase in hypertensives. 5. Total peripheral resistance was inappropriately elevated in hypertensive pregnancy, but was normalized in the oxprenolol-treated group. 6. There was no reduction in heart rate or cardiac output in the beta-adrenoreceptor blocker-treated group. This feature, in combination with lowered peripheral resistance, may contribute to the improvement in foetal outcome observed in maternal hypertension of pregnancy treated with oxprenolol.
1. Venous compliance and plasma volume were measured in thirty-one continuously normotensive women early (11-20 weeks) and late (31-40 weeks) in pregnancy and following delivery. 2. Mathematically fitted pressure/volume curves, obtained by venous occlusion plethysmography, were analysed according to two describing functions (i) the peak of the first derivative dv/dp max and (ii) a work index, integral of 25 (10) p dv. 3. The relationship between venous/volume factors seen after delivery, was disturbed during pregnancy, at which time the work index provided evidence for decreased venous compliance. 4. Pregnancy could be regarded as a potentially hypertensive state, brought about by a vascular/volume mismatch.
The pattern of phasic pressure and flow in an artery is related to the components of the impedance of that artery and hence to its compliance. Phasic patterns of velocity in peripheral arteries have been recorded by using continuous wave ultrasound Doppler flowmeters coupled to high-speed spectrum analysers; this has enabled display of the stored spectral ensembles as 'sonograms'. Simultaneous recordings at proximal and distal sites in each limb of a variety of subjects were made under standard resting conditions; characteristic patterns of change in the sonogram are recognized where gross abnormalities of arterial anatomy are present. A technique is under development whereby the mean values of velocity for each 7.4 ms time slice are derived, smoothed, and the pulse described by standard Fourier transform analysis. The change of the waveform occurring during passage through the relevant arterial segment is then described by comparing the amplitude/frequency and time-delay/frequency plots at proximal and distal sites. Although results are at present preliminary, changes relating to age and known vascular abnormality are becoming apparent. Further development is in progress to determine the significance of these findings.
Capillary permeability (CP) is elevated in late normal pregnancy, when compared to postpartum values. In women with pregnancy associated hypertension (PAH), pregnancy CP levels are not different from postpartum and are less than in normal pregnancy. These changes in capillary permeability are not explained by alterations in serum albumin.
Blood pressure variation over 24 h was studied in twelve subjects with suspected or established autonomic failure using ambulatory intra-arterial monitoring. Three subjects who had been previously diagnosed as having orthostatic hypotension due to autonomic failure were found to have normal circulatory reflexes. A generally consistent circadian variation of blood pressure was seen in the other nine subjects, pressure rising gradually from its lowest point early in the morning to a peak during the early part of the night; this pattern was also found during bed rest in four subjects. Supine hypertension (an hourly mean blood pressure of greater than 170/90 mmHg) not suspected from sphygmomanometric readings was observed in four subjects, generally during the night. Heart rate variability was reduced in six subjects while short-term blood pressure variability was markedly increased.
Short-term salt loading and salt restriction in a group of normal pregnant women produced no changes in lying, sitting or standing blood pressures or heart rates. Home blood pressures showed no trend to change over the periods of altered salt intake. Although plasma volume and plasma renin activity changed with altered salt intake, there were no relationships between changes in these parameters and changes in mean arterial pressures (MAP) between the low and high salt diets. Capillary permeability and echocardiographic dimensions were unchanged by salt intake once sodium balance had been established.
Cardiovascular adaptations to the circulatory and volume changes of pregnancy have been studied in late normal and hypertensive pregnancy and postpartum. There has been evidence of a marked plasma volume expansion in normal pregnancy, blunted in preeclampsia; an increased capillary permeability during normal pregnancy; augmented left ventricular mass, which is increased in mild preeclampsia; and similar increases in peripheral venous distensibility during normal and preeclamptic pregnancy. In mild preeclampsia the enlarged ventricle has been shown to be capable of maintaining a normal cardiac output despite elevated afterload. The forearm vascular bed appears to play little part in these adjustments, because forearm venous distensibility has been shown to be higher during normal pregnancy than during postpartum; in hypertensive individuals there was no difference during pregnancy and postpartum. It is evident from this brief review that it is too early to draw clear-cut conclusions regarding the vascular, volume, and cardiac response to normal and hypertensive pregnancy. Research in this field, including two-dimensional echocardiography and plethysmography in larger homogeneous groups, will probably lead to a better understanding of the pathophysiological mechanism of pregnancy hypertension.
Similarities in coronary circulation and heart size of sheep to that of humans are specific advantages of a sheep model of congestive heart failure (CHF). CHF was created in 11 sheep (51 +/- 4 kg) by selective sequential intracoronary injection of 90 microns microspheres under 1.5% isoflurane anesthesia. Hemodynamic characteristics were assessed at baseline, 4 weeks after establishment of CHF (ejection fraction [EF] < 35%, n = 11), and 26 weeks (n = 7) later. Baseline echocardiographic EF was 59 +/- 5% and fell to 26 +/- 5% after 5 +/- 2 embolizations. The left ventricular (LV) pressure-volume relationship showed stable decreases in LV end-systolic elastance (Ees) and preload recruitable stroke work. Intravenous infusion of dobutamine increased Ees from 2.8 +/- 1.7 to 4.3 +/- 2.2 and 4.5 +/- 1.4 mmHg/ml at heart rates of 140 and 160/min, respectively, at baseline. Increases of Ees (from 1.3 +/- 0.5 to 2.3 +/- 0.7 and 1.9 +/- 0.5 mmHg/ml at heart rates of 140 and 160/min, respectively) with dobutamine under CHF conditions did not exceed Ees values at baseline without dobutamine. This response to dobutamine infusion did not change 26 weeks after establishment of CHF. This stable ovine CHF model is proposed for studies on the long-term effects of cardiac assist devices.