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Biomedical subjects

J M Pfeffer

Publications and source records attributed to J M Pfeffer.

At least 19 recordsLinked to original sources
PubMed1991

Progressive ventricular dilation in experimental myocardial infarction and its attenuation by angiotensin-converting enzyme inhibition.

The extent to which the impaired left ventricle dilates may have important prognostic implications for survival. To determine the influence of infarct size and duration on ventricular dilation, the passive pressure-volume relation of the left ventricle in the rat after coronary artery ligation was obtained. In the early (0.25 to 2 days) phase, the pressure-volume relation was relatively unchanged in all infarct-size groups, except for a rightward shift in the low pressure range for moderate and large infarcts and a leftward shift in the high pressure range for small infarcts. From 2 to 7 days, ventricular dilatation occurred in all groups in relation to infarct size. Thereafter (to 106 days), in rats with moderate and large infarcts, the left ventricle continued to dilate. Associated with this late dilation was a decrease in left ventricular chamber stiffness and an increase in the volume to mass ratio. To determine whether the potentially deleterious progression of ventricular dilation could be attenuated, the angiotensin-converting enzyme inhibitor captopril was given 2 or 21 days after infarction and continued for 3 months. There was a significant overall effect of this treatment in attenuating left ventricular dilation, which was most pronounced in moderate infarcts. Captopril not only attenuated the rightward shift of the pressure-volume relation, but also markedly lowered left ventricular filling pressures so that operating volumes in treated rats were considerably reduced compared with those in untreated rats, even in large infarcts. Therapy with captopril also had an overall effect in prolonging survival, the most benefit being observed in moderate infarcts with lesser dilated left ventricles.

Analysis of Variance↗
PubMed1991

Progressive ventricular remodeling in rat with myocardial infarction.

Ventricular dilatation may have important prognostic implications for the survival of patients with left ventricular (LV) dysfunction. To determine the manner and extent to which the left ventricle of the rat remodels and dilates after myocardial infarction, we obtained the passive pressure-volume relationships, chamber stiffness constants, and mass during both the early and late phases. In moderate and large infarcts as inflammation and edema developed, LV weight increased then progressively decreased as a thin scar formed, returning to normal values as a result of compensatory hypertrophy of the residual myocardium. LV dilatation occurred in all rats with infarcts but to different extents depending on infarct size and duration. In the early postinfarction phase, pressure-volume relationship was relatively unchanged in all infarct-size groups, except for significant rightward shift in low pressure range for rats with moderate and large infarcts and significant leftward shift in high pressure range for rats with small infarcts. During resolution of the inflammatory response, LV dilatation occurred in all infarct groups in relation to infarct size. As scar formation became complete, LV enlargement did not progress in rats with small infarcts but did so in rats with moderate and large infarcts. LV chamber stiffness remained within the range of normal values during the early phase in all rats with infarcts but decreased significantly during the late phase in rats with moderate and large infarcts in association with the extent of ventricular enlargement. Alterations in the volume-to-mass ratio (V/Vwt) were most marked in the late postinfarction phase, wherein both volume (increased) and mass (decreased, then increased) changed dramatically and V/Vwt progressively increased in rats with large infarcts.

Animals↗
PubMed1990

Systemic hemodynamic effects of endothelin in rats.

Endothelin type 1 (ET-1) is an endothelial cell-derived 21-amino acid peptide with potent contractile effects on isolated vascular smooth muscle. The systemic hemodynamic effects of bolus intravenous injections of ET-1 and angiotensin II (ANG II, 300 pmol) were examined in anesthetized male Munich-Wistar rats by measurements of mean arterial (AP) and right atrial (RAP) blood pressures and cardiac index (CI, electromagnetic flowmetry) over a 60-min period. ET-1 induced a biphasic pressure response: transient hypotension occurred in the early phase with all doses, followed by a more prolonged dose-dependent elevation of blood pressure in the late phase. Because CI was unchanged during the early phase, the hypotension resulted from systemic vasodilation. On the other hand, the marked rise in AP produced by 300 pmol of ET-1 in the late phase was associated with a significant fall in CI, and thus total peripheral resistance index (TPRI) increased profoundly. A fall in right atrial pressure and significant hemoconcentration were associated with this pronounced vasoconstrictor effect, suggesting that a contraction of plasma volume contributed to the reduction of CI. Additionally, stroke and minute work indexes and peak flow velocity became significantly reduced in the late phase for the 300-pmol dose of ET-1. When compared with an equimolar dose of ET-1, 300 pmol of ANG II produced a prompt, more marked, but shorter-lived rise in AP with minimal changes in CI, TPRI, RAP, and hematocrit. These results raise the intriguing possibility that endothelin may play a role in both the control of normal vascular smooth muscle tone and in the pathogenesis of vasospastic disorders.

Angiotensin II↗
PubMed1988

Angiotensin converting enzyme inhibition and ventricular remodeling in heart failure.

The prevention or attenuation of the development of heart failure by the angiotensin converting enzyme inhibitor captopril was examined in two animal models, spontaneously hypertensive rats and rats with myocardial infarction produced by coronary artery ligation. In 24-month-old female spontaneously hypertensive rats with marked left ventricular hypertrophy, cardiac output was reduced despite an increase in ventricular volume, resulting in a greatly reduced ejection fraction. Treatment with captopril from 14 to 24 months of age maintained forward output and prevented ventricular dilatation so that ejection fraction remained normal; left ventricular hypertrophy regressed to levels observed in six-month-old spontaneously hypertensive rats. In rats with moderate and large infarcts three months after ligation, left ventricular filling pressures were elevated, forward output was reduced, and ventricular volumes were greatly increased. Long-term therapy with captopril maintained filling pressures within normal limits and maintained forward output from a lesser dilated left ventricle to yield an ejection fraction that was elevated compared with that in untreated rats. Thus, the potentially deleterious remodeling of the left ventricle in heart failure, an extensive increase in mass and chamber volume, can be favorably altered by long-term angiotensin converting enzyme inhibition (captopril) with salutary effects on hemodynamics.

Animals↗
PubMed1988

Atrial natriuretic factor gene expression in ventricles of rats with spontaneous biventricular hypertrophy.

A subset of Wistar-Kyoto (WKY) rats that spontaneously develops biventricular hypertrophy (BVH) in response to increased cardiac output was evaluated for ventricular expression of the atrial natriuretic factor (ANF) gene. Normal WKY rats had low levels of left ventricular ANF mRNA and minimally detectable ANF transcripts in the right ventricle. In contrast, BVH rats showed a sixfold greater ANF mRNA concentration in the left ventricle than age-matched WKY controls. BVH right ventricular ANF mRNA levels equaled those found in BVH left ventricles and were dramatically greater than WKY right ventricular controls. Unlike experimental models of hypertrophy, both left and right ventricles significantly increase ANF gene transcripts in the natural development of BVH. The left and right ventricles can concordantly respond to hypertrophy and increase ANF gene transcription.

Animals↗
PubMed1988

Papillary muscle structure-function relations in the aging spontaneously hypertensive rat.

Isolated left ventricle papillary muscle mechanics and structure were studied in male spontaneously hypertensive (SHR) rats and two control groups of animals, the normotensive Wistar (NR) and the Wistar-Kyoto rat (WKY). Active tension and its first derivative (dT/dtmax) normalized for muscle cross-sectional area were increased in preparations from the SHR at all ages studied relative to control groups (P less than 0.01). However, when these parameters were normalized for myofibrillar cross-sectional area determined from electronmicroscopic point counting data, differences between groups were no longer significant. Force-velocity relations provided no evidence for a depression of shortening velocity at any load in the SHR at any age relative to the two control groups. The duration of mechanical activity, as determined by time-to-peak isometric tension and analysis of muscle force-velocity-time relations, was prolonged only in the 18 month old SHR (P less than 0.01). Thus, while changes in isolated muscle performance occur at a time when hemodynamic impairment is reported in the intact animal (male 18 month SHR), no evidence for depression of isolated muscle function is seen in the SHR at 6, 12 or 18 months of age.

Age Factors↗
PubMed1987

Atrial natriuretic peptide transcription, storage, and release in rats with myocardial infarction.

To study the role of atrial natriuretic peptide (ANP) in chronic heart failure, ANP synthesis, storage, and release were examined by measuring atrial ANP messenger ribonucleic acid (mRNA) levels and atrial and plasma ANP concentrations in rats with myocardial infarction produced by coronary artery ligation. Three groups were defined as the following: 1) controls, sham-operated, or operated, but noninfarcted; 2) moderate infarcts, involving 5-30% of the left ventricular circumference; and 3) large infarcts (greater than or equal to 30%). In addition, to determine a possible modulation by dietary Na intake on ANP levels in heart failure, plasma immunoreactive ANP (iANP) levels were measured in rats with and without infarcts given low, regular, or high Na intake for 2 wk, by which time all groups were in neutral balance. Plasma iANP levels varied directly with increasing infarct and atrial sizes, irrespective of Na intake. In contrast, atrial ANP concentration varied inversely with increasing infarct size. The ANP mRNA content index, a measure of total atrial ANP mRNA, was significantly increased in rats with large infarcts compared with control rats. These results indicate that in rats with myocardial infarction, the severity of left ventricular dysfunction, as inferred from infarct size, but not chronic Na intake, is the primary determinant of the extent of activation of the ANP system. Elevated circulating ANP levels are maintained through enhanced atrial synthesis and release. ANP may thus play an important role in the hemodynamic and renal adaptations to chronic heart failure.

Animals↗
PubMed1987

Plasma nonesterified fatty acids in the Dahl rat. Response to salt loading.

The link between dietary salt intake and the development of hypertension in the salt-sensitive Dahl strain of rats remains elusive. There is evidence that Dahl salt-sensitive rats (DS) produce less vasodilator and natriuretic prostaglandins in response to salt loading than do control salt-resistant rats (DR), although the reason for this blunted response is unknown. We examined the effects of chronic dietary salt loading on the plasma levels of nonesterified fatty acids in DS and DR. Animals were fed the same chow containing either 0.4% or 4% NaCl (wt/wt). At 12 weeks, 75 microliters of tail capillary blood was obtained from restrained, conscious rats, and principal nonesterified fatty acids were measured by high performance liquid chromatography. Total nonesterified fatty acids rose in the 15 DR on high salt diets compared with values in 11 rats eating low salt (0.57 +/- 0.05 vs 0.35 +/- 0.01 mM; p less than 0.001). The greatest changes occurred in levels of arachidonic acid (+287%) and in the arachidonic precursors, linoleic (+89%) and linolenic (+107%) acids. In marked contrast, there was no change in levels of plasma nonesterified fatty acids in DS fed 4% NaCl compared with DS fed 0.4% NaCl. These observations suggest that defective production of natriuretic and vasodilator prostaglandins by DS may be due in part to an inability to produce or release eicosanoid precursors from phospholipid stores in response to dietary salt.

Animals↗
PubMed1987

Ventricular enlargement and reduced survival after myocardial infarction.

Increased ventricular volume is one of the most powerful predictors of reduced survival in patients with heart disease. Despite its well-documented prognostic significance, the magnitude of the progression of ventricular dilatation from the acute to the chronic phase of myocardial infarction has only recently been appreciated. In an experimental preparation of myocardial infarction in rats, left ventricular cavitary volume increased progressively even after histologic resolution of the infarct region. We hypothesized that this remodeling of the infarcted left ventricle was a response to an increase in both systolic and diastolic wall stresses and that captopril, by reducing wall stress, would attenuate the process. For comparably sized infarcts, the captopril-treated rats had smaller ventricular volumes at common distending pressures, yet they had maintained or improved cardiac output. Most importantly, long-term captopril therapy also prolonged the survival of these rats with experimental myocardial infarction. The implication of these animal studies is that the potential exists for the attenuation of progressive ventricular enlargement and improvement of survival of patients recovering from a myocardial infarction. At the present time, no information is available in patients as to the therapeutic potential of interrupting this insidious process of ventricular dilatation in order to improve survival. Clinical trials are required to determine whether salutary benefits similar to those observed in animals can be provided to patients recovering from a myocardial infarction.

Animals↗
PubMed1987

Hemodynamic benefits and prolonged survival with long-term captopril therapy in rats with myocardial infarction and heart failure.

To determine whether the hemodynamic profile of chronic heart failure secondary to myocardial infarction could be altered, captopril was administered to female Wistar rats 3 weeks after coronary artery ligation and continued for 3 months. Captopril reduced left ventricular mass, prevented the increase in right ventricular mass observed with increasing infarct size, lessened the increase in left ventricular end-diastolic pressure, and reduced mean arterial pressure and total peripheral resistance, whereas cardiac output and heart rate were maintained. The end-diastolic volume of treated rats with moderate infarcts was significantly less than that of untreated rats, and therefore the ejection fraction index was significantly increased. In rats given captopril until death or for a period of up to 1 year, survival was significantly prolonged, particularly in those rats with moderate-sized infarcts.

Animals↗
PubMed1986

Altered sensitivity to increases in vascular resistance in rats with hypertension and myocardial infarction.

Left ventricular dysfunction reduces the ability of the heart to maintain forward output when subjected to the additional stress of an increased vascular resistance. To determine the extent to which hearts from rats with both hypertension and myocardial infarction are sensitive to increases in vascular resistance, spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR) with and without myocardial infarction (coronary artery ligation) were infused with methoxamine (0.08 to 1.6 mg/kg/min). Mean arterial pressure during methoxamine infusion was significantly lower in infarcted rats than in noninfarcted rats in each strain, due largely to a lower cardiac output in infarcted rats. When compared at equal pressures, the infarcted groups of each strain generated a lower cardiac output than did the respective noninfarcted groups, as a result of both a lower stroke volume and heart rate. During the methoxamine infusion, absolute pressure levels in SHR with large infarcts were similar to those in NWR. Thus, infarcted hearts from both hypertensive and normotensive rats, when subjected to the stress of an increase in vascular resistance, demonstrated an impairment of pumping ability that was related to the extent of left ventricular damage. Impaired pressure-generating capacity was most pronounced in SHR with large infarcts, which were unable to generate hypertensive levels of blood pressure.

Animals↗
PubMed1986

Renal and systemic hemodynamic effects of synthetic atrial natriuretic peptide in the anesthetized rat.

To characterize the hemodynamic events responsible for alterations in renal function during administration of atrial natriuretic peptide, we studied the systemic, renal, and glomerular circulatory effects of intravenous rANP[126-149], administered as a 4 micrograms/kg prime and 0.5 microgram/kg per minute continuous infusion in anesthetized, euvolemic rats. With this protocol, a small decline in mean systemic arterial blood pressure occurred in the context of markedly enhanced urinary sodium excretion, hemoconcentration, and reduced left ventricular end-diastolic pressure and +dP/dt. However, despite a significant decrement in renal vascular resistance, total peripheral resistance remained constant, thereby denoting a preferential renal vasodilatory effect of this peptide in vivo. Whole kidney and single nephron GFR increased by approximately 20%, while effective renal and glomerular plasma flow rates remained stable, resulting in a substantial rise in filtration fraction. Of all the parameters potentially capable of augmenting single nephron GFR, only glomerular capillary hydraulic pressure increased significantly and therefore accounted entirely for the hyperfiltration observed during ANP infusion. This rise in glomerular capillary pressure, in turn, resulted from afferent arteriolar vasodilatation and concurrent efferent arteriolar vasoconstriction, findings that proved independent of both endogenous angiotensin II activity and ANP-induced reductions in renal perfusion pressure. These renal hemodynamic effects are unique when compared with actions of previously studied renal vasodilatory agents.

Anesthesia, General↗
PubMed1986

The behavioural approach in medical practice.

This paper gives a description of the behavioural approach, behaviour therapy, and behavioural medicine in a medical and general hospital setting and describes the intimate link between behaviour and illness, showing how knowledge of the way learning takes place and influences behaviour can lead to a better understanding of the aetiology of illness and thus to appropriate treatment. A behavioural approach can be applied to the understanding and treatment of medical problems associated with sphincteric disturbances, such as childhood encopresis and urinary retention, as well as to the improvement of patient compliance and to the better management of pain. In the field of preventive medicine this approach is of importance in modifying behaviour associated with cardiovascular disorders, obesity, and smoking.

Adult↗
PubMed1985

Left ventricular hypertrophy and pressure generating capacity in aging genetically hypertensive rats.

Alterations in the relationship between the degree of left ventricular hypertrophy and the maximum pressure generating capacity were assessed in two models of genetic hypertension in rats. Both the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive (DS) rat developed systemic hypertension and progressive increases in left ventricular mass. In the DS rat, the magnitude of the hypertension and ventricular hypertrophy produced was in direct relation to the level of dietary sodium intake. At 6 months of age, the pressure generating capacity of all hypertensive rats was directly related to the left ventricular weight/body weight ratio. With the moderate level of hypertrophy observed in the 12-month-old SHRs and DS rats on a low salt diet, the correlation between left ventricular weight and augmented pressure generating capacity during isovolumic contractions was maintained. With the more severe degrees of left ventricular hypertrophy observed in 18- and 24-month-old SHRs and 12-month-old DS rats on a moderate salt diet, the further addition of ventricular mass was no longer associated with a proportional augmentation in maximal pressure development. These studies suggest that in genetic hypertension in rats, both the magnitude and duration of the hypertension are important determinants of the degree of hypertrophy and the functional status of the ventricle.

Age Factors↗