Biomedical subjects

S E Downing

Publications and source records attributed to S E Downing.

At least 37 records · Page 2Linked to original sources

PubMed1986

Ventricular performance in diabetic rabbits with norepinephrine cardiomyopathy.

The purpose of this investigation was to examine the effects of norepinephrine cardiomyopathy (NE-CM) on left ventricular (LV) performance in diabetic rabbits. Diabetes mellitus was produced in 11 rabbits by giving them alloxan monohydrate, 120 mg/kg. Cardiomyopathy was produced in five animals by a 90-min infusion of norepinephrine (2 micrograms/min/kg). Left ventricular contractility and pump function (VF) were examined 2 days later. The effects of hypercapnia and inotropic responsiveness to NE were also determined. VF was assessed by means of left ventricular function curves obtained with constant mean aortic pressure and heart rate and quantified by determining stroke volume (SV) at a left ventricular pressure of 10 cm H2O (SV10). Mean SV10 was 1.22 +/- 0.08 ml in control diabetics but averaged only 0.95 +/- 0.08 ml in diabetics with NE-CM (P less than 0.05). NE-CM markedly reduced LV dP/dt max responses to NE infusion but the increments in SV10 did not differ. Hypercapnia caused significantly greater ventricular depression in NE-CM than in control diabetic rabbits (P less than 0.001). The depressive effect of hypercapnia can be countered in part by the administration of NE in both groups, but differential depression in VF to hypercapnia was persistent between the two groups.

Animals↗

PubMed1985

Potentiation by calcium channel blockade of hypoxic myocardial depression in the neonate.

The objectives of this study were to examine the independent and combined effects of beta blockade (practolol) and calcium channel blockade (verapamil) on cardiac responses to hypoxia in the neonate. Lambs were anaesthetized with pentobarbital (20 mg/kg) and were prepared for measurements of left ventricular (LV) performance under controlled hemodynamic conditions. Force generation was assessed from curves relating LV systolic pressure (SP) to end-diastolic pressure (LVEDP) over a broad range of afterloading. Velocity was determined from simultaneous measurements of LV dP/dtmax. Values obtained at LVEDP 10 cm H2O were used to compare interventions. Practolol (P) caused no significant reduction in SP10, but dP/dt10 fell from 51 to 37 (X 10(2] mm Hg/sec (p less than 0.05). Verapamil (V), 2 micrograms/min/kg, reduced measures of contractility (p less than 0.01). Doubling the dose of V further reduced SP10 to 79% of control. Hypoxemia (PaO2, 32 torr) increased SP10 from 172 to 192 mm Hg, and dP/dt10 from 51 to 85 (X 10(2] mm Hg/s (p less than 0.001). After P, the same degree of hypoxia elicited no changes in LV function. During infusion of V (4 micrograms/min/kg), hypoxia reduced SP10 from 138 to 122 mm Hg (p less than 0.01) and dP/dt10 from 29 to 24 (X 10(2] mm Hg/sec (p less than 0.05). It is concluded that in the absence of adrenergic support, hypoxia significantly depresses both force and velocity parameters of contractility in hearts with calcium channel blockade.

Animals↗

PubMed1985

Coronary vasoconstriction and catecholamine cardiomyopathy.

Norepinephrine (NE) causes extensive myocardial injury in the rabbit. To investigate a potential mechanism we measured coronary blood flow with radioactive microspheres. Coronary resistance and oxygen demand (heart rate-blood pressure double product) were calculated. Severity of injury was determined by semiquantitative histologic evaluation. Changes resulting from NE infusion were determined in animals with or without alpha-receptor blockade with phentolamine (10 mg). In all animals oxygen demand remained constant. Coronary blood flow (ml/gm/min) was 2.66 at the beginning of the experiment, rose to 3.46 after 3 minutes of NE infusion (p less than 0.05), then declined to baseline values (2.33) after 10 minutes. However, coronary blood flow was sharply lower than baseline (1.51; p less than 0.05) after 40 minutes of infusion. Coronary resistance rose progressively from baseline values of 40.9 (units) to 74.8 at 40 minutes (p less than 0.05). Animals given phentolamine manifested none of these changes. Control subjects infused with saline solution showed no significant changes in coronary blood flow or coronary resistance. Animals pretreated with phentolamine had minimal histologic damage at 48 hours compared with NE alone (p less than 0.01). We conclude that NE induces sustained coronary vasoconstriction in the rabbit and that reduced coronary blood flow may contribute to the pathogenesis of NE cardiomyopathy in this species.

Animals↗

PubMed1985

Myocardial injury following endogenous catecholamine release in rabbits.

Catecholamines (CAT) given in large doses produce cardiomyopathic changes in several animal species. This study was designed to determine if endogenous release can also induce cardiac injury. Rabbits were infused with doses of tyramine (TYR), ranging from 200 to 500 micrograms/min/kg, i.v. for 90 min. Arterial pressure and heart rate were measured, as were total CAT concentrations, blood gases, pH and glucose. Two days later the animals were killed and cardiac injury assessed using a histological scoring system. All data were compared with controls given saline. Initial CAT averaged 452 pg/ml, rose to 2890 pg/ml after starting TYR, 500 micrograms/min/kg, and remained elevated for the duration of infusion. Circulating CAT levels were a function of TYR dose, and bore a linear relationship to the histological score (P less than 0.001). Development of lesions was unaltered by beta 1 blockade with practolol, but sharply reduced by alpha blockade with phentolamine (P less than 0.01). Pretreatment with insulin also reduced lesion formation, but diabetic (alloxan) rabbits showed no greater CAT injury. It is concluded that endogenous release of CAT induces myocardial injury in the rabbit in a dose-dependent manner. This is unrelated to myocardial O2 demand, and microvascular pathology was absent. Activation of alpha adrenergic pathways is likely the dominant or exclusive mechanism.

Animals↗

PubMed1985

Enhanced adrenergic sensitivity of the diabetic neonatal heart.

We have previously shown that insulin reduces inotropic responses to norepinephrine (NE) in isolated cardiac muscle and intact hearts. This inhibition also occurs in vascular smooth muscle. The present study was designed to examine inotropic sensitivity of insulin-deficient diabetic (D) hearts to mixed (NE) and pure beta 1 (isoproterenol, Iso) adrenergic agonists. Lambs were given alloxan (150 mg/kg) and studied 2 days later (glucose, 392 mg/dl). Results from eight controls (C) were compared. All animals were prepared for measurements of ventricular performance and coronary flow (CF) under conditions of constant arterial pressure, aortic flow, and heart rate (paced). Dose-response dP/dtmax curves were obtained by stepped increases of agonist infusion (iv). Iso (40 ng X min-1 X kg-1) caused a 30% increase of CF in both C and D, but no change occurred with NE (0.4 micrograms X min-1 X kg-1). Myocardial O2 consumption did not differ among groups and was unaltered by either agonist. Initial values for heart rate and dP/dt did not differ between C and D. NE dose-response curves were consistently higher in D and the slopes significantly steeper than C. However, Iso curves did not differ. Insulin (10 U/kg) was given to both groups, and the studies were repeated. Dose-response curves in C did not differ significantly with either NE or Iso after insulin. In contrast, curves with both agonists were lower following insulin replacement in the diabetic animals. It is concluded that coronary resistance is reduced by beta-activation but unchanged by NE, which is also an alpha-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Restoration of coronary dilator action of adenosine in experimental diabetes.

We have recently shown that the coronary dilator action of adenosine is reduced in animals with experimental diabetes mellitus. Effects of insulin replacement are reported in the present study. Lambs, age 6-17 days, were studied 1-2 days after induction of diabetes with alloxan (150 mg/kg; n = 6). These were compared with nondiabetic controls, age 4-15 days (n = 5). A third group was studied after 8-15 days of diabetes (n = 3). In the acute diabetics blood glucose was 362 +/- 48 mg/dl. Heart rate, dP/dtmax, and myocardial O2 consumption did not differ from controls, but pH tended to be lower (7.29 +/- 0.03). Adenosine was given by left ventricular infusion. Coronary flow changes were significantly lower at all infusion rates (3-15 micrograms X min-1 X kg-1) in the untreated diabetics. Dose-response curves before and after insulin (10 U/kg) were identical in controls. However, in the diabetics, insulin enhanced the dilator response to adenosine, and changes in coronary flow at each infusion rate did not differ from controls. Aminophylline (6 mg/kg) abolished or sharply reduced the dilator responses to adenosine in both controls and diabetics (P less than 0.01). Animals diabetic 1-2 wk were unresponsive to adenosine. But after insulin, the nucleoside elicited vigorous coronary dilatation. It is concluded that insulinopenic diabetes is accompanied by sharply reduced adenosine sensitivity of coronary resistance vessels. Sensitivity is restored by giving insulin. This hormone may modulate adenosine receptor properties of vascular smooth muscle.

Adenosine↗

PubMed1983

Analysis of cardiac adrenergic mechanisms in hypoxic lambs.

Adrenergically mediated inotropic and chronotropic responses to hypoxemia were studied in 12 neonatal lambs ranging from 1 to 10 days of age. Six lambs were adrenalectomized (Adnx) and six were sham operated. Inotropic changes were assessed from measurements of left ventricular dP/dtmax under controlled hemodynamic conditions. Atropine (1 mg) was given and hypoxia produced by adding N2 to the respirator. In the sham-operated lambs, dP/dtmax increased as a function of the level of hypoxemia. With a mean arterial O2 partial pressure (PaO2) of 21.7 +/- 2.0 Torr, dP/dtmax averaged 17 X 10(2) mmHg/s above control values. Adnx did not reduce resting dP/dtmax, but comparable levels of hypoxemia elicited a much smaller increase (5 X 10(2) mmHg/s) in this group (P less than 0.02). In the sham-operated lambs, ganglionic blockade with tetraethylammonium chloride (TEAC, 100 mg) reduced the hypoxic response to similar values (6.5 X 10(2) mmHg/s). These residual inotropic responses were completely abolished by beta-adrenergic blockade with practolol (4 mg/kg). Chronotropic changes were identical in both groups (18.7 beats/min) and abolished by TEAC alone. It is concluded that the major fraction of adrenergic inotropic stimulation during hypoxemia is derived from the adrenal glands and that autonomic neural function is essential to the release process. Heart rate responses are independent of adrenal integrity. A residual source of inotropic stimulation, blocked by practolol, is derived from unidentified sources.

Adrenalectomy↗

PubMed1983

Enhanced sensitivity of diabetic hearts to alpha-adrenoceptor stimulation.

Inotropic responses to alpha-adrenergic stimulation with methoxamine were compared in 12 normal (N) and 12 diabetic (Db) lambs. Diabetes was produced by giving alloxan monohydrate (150 mg/kg iv). Measurements of maximal rate of rise of left ventricular pressure (dP/dtmax), left ventricular end-diastolic pressure (LVEDP), coronary flow, and myocardial O2 consumption were made simultaneously in hemodynamically controlled preparations. All animals were subjected to ganglionic blockade (tetraethylammonium chloride, 100 mg) and beta1-adrenergic blockade (practolol, 4 mg/kg). Methoxamine was given in incremental doses ranging from 0.4 to 6.0 mg/kg. dP/dtmax increased progressively to 126 +/- 4% of initial values in N. However, the increase was twice as large (150 +/- 4%) in the diabetics (P less than 0.005). LVEDP fell in both groups. These changes were abolished by phentolamine (2 mg/kg). Inotropic responses to methoxamine in lambs 2 and 3 wk after induction of diabetes did not differ from those with acute (2 days) diabetes. Dose-response curves obtained by infusing Ca2+ (2-8 mg X min-1 X kg-1) were identical in N and Db. It is concluded that lamb myocardium possesses an alpha-adrenergic receptor system that is stimulated by methoxamine in a dose-dependent manner and blocked by phentolamine. Db hearts are supersensitive to alpha-receptor activation. The mechanistic basis for this latter finding has not been examined but may relate to altered receptor density or nucleotide regulation.

Animals↗

PubMed1983

Contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine cardiomyopathy.

Graded doses of norepinephrine and methoxamine were given to rabbits over a standard 90-minute infusion period to assess their potential for inducing myocardial injury. Lesions of myofiber necrosis and leukocytic infiltration were graded semiquantitatively in animals killed 2 days later. A close correlation was found between the dose of norepinephrine and the histological score (r = 0.912, P less than 0.001). Mean arterial pressure rose from 100 mm Hg to a maximum of 129 mm Hg, and averaged 115 mm Hg during infusion of 2 micrograms/min per kg. However, heart rate fell from 287 beats/min to average 208 beats/min. The pressure-rate product, an index of metabolic demand, showed no significant change and did not differ from saline-infused controls. Beta-adrenergic blockade with practolol (4 mg/kg) or propranolol (1 mg/kg) failed to significantly reduce cardiac injury with norepinephrine. However, alpha-adrenoceptor blockade with phentolamine (10 mg), alone or in combination with either of the beta-antagonists, markedly reduced lesion formation as reflected by the histological score (P less than 0.02). Administration of the alpha-agonist methoxamine produced dose-related increases in the intensity of myocardial injury (r = 0.938, P less than 0.01), morphologically identical with those resulting from norepinephrine. Hemodynamic changes also were comparable. Phentolamine markedly reduced methoxamine injury. It may be concluded from these studies that norepinephrine cardiomyopathy results in large part from activation of the alpha-adrenergic system in the rabbit model. Ischemia or a supply-demand mismatch are unlikely mechanisms. We speculate that alterations in myofiber Ca++ translocation, uptake, and binding induced by alpha 1-receptor activation may contribute to membrane damage.

Adrenergic alpha-Antagonists↗

PubMed1983

Effects of hypercapnia on myocardial contractility in piglets.

The effects of acute hypercapnia on cardiac contractility and their dependence on adrenergic pathways were studied in 27 piglets anesthetized with pentobarbital (30 mg/kg, ip). Aortic pressures and flow, and heart rate were held constant; atropine was used to produce parasympathetic blockade. Hypercapnia was achieved by addition of CO2 to the respirator. In the control group (N = 7) the first derivative of left ventricular (LV) pressure (dP/dtmax) increased significantly following induction of severe hypercapnia (PaCO2 greater than 80 mm Hg; pH less than 7.00). There were no significant changes in LV end diastolic pressure. The magnitude of the positive inotropic responses was unaltered by ganglionic blockade with tetraethylammonium chloride (100 mg) (N = 5). In contrast, no change in LV dP/dtmax was observed during hypercapnia in piglets (N = 15) subjected to beta-adrenoreceptor blockade with practolol (4 mg/kg). Our findings indicate that the increased cardiac contractility during acute severe hypercapnia is not dependent upon the integrity of the neural reflex system. Rather, it is due to adrenal release of catecholamines into the circulation. These animals are highly resistant to the intrinsic cardiac depressant action of hypercapnic acidosis.

Acidosis↗

PubMed1983

Cardiac dimensions in severely anemic neonatal pigs.

The effects of chronic severe anemia on weights and chamber volumes of hearts were studied in 9 spontaneously anemic neonatal pigs (mean hematocrit = 10.1%) and 10 healthy piglets (mean hematocrit = 28.3%) of approximately the same age and similar body weights. All cardiac chamber weights, as well as total heart weight/body weight ratios, were significantly higher in the anemic pigs than in the healthy pigs (P less than 0.001). The left ventricular free wall/right ventricular free wall weight ratio was identical in the 2 groups. Calculated left ventricular volume/body weight ratio also was significantly greater in the anemic pigs (P less than 0.05). It is concluded that cardiac dilatation and hypertrophy occur consistently in chronically anemic neonatal pigs. These changes are independent of age or body weight of the animal.

Anemia↗

PubMed1982

Four-valve polymicrobial endocarditis caused by Pseudomonas aeruginosa and Serratia marcescens.

This report describes what is believed to be the first case of mixed Pseudomonas and Serratia endocarditis, of probable nosocomial etiology, with involvement of all four heart valves in a 56 year old nonaddicted patient. Although both organisms were recovered in culture, infection and tissue invasion were documented by light and electron microscopy. The clinical course in this patient differed from more typical patterns of Pseudomonas or Serratia endocarditis that have been observed as complications of narcotic addiction or compromised cardiac status. Our patient had the rare occurrence of endocarditis with two organisms and four-valve involvement. Clinically, however, this presented as a right-sided endocarditis and behaved as though only a single organism were present.

Endocarditis, Bacterial↗

PubMed1982

Ventricular function in norepinephrine-induced cardiomyopathic rabbits.

Catecholamine cardiomyopathy (CM) was produced in rabbits by a 90-min infusion of norepinephrine (NE, 2 micrograms . kg-1 . min-1). Left ventricular (LV) contractility and pump function (VF) were examined 2 days later and compared with control animals. The effects of hypercapnia [CO2 tension (PCO2) greater than 70 mmHg] and inotropic responsiveness to NE were also determined. VF was assessed by means of left ventricular function curves obtained with constant aortic pressure and heart rate and quantified by determining stroke volume at left ventricular end-diastolic pressure of 10 cmH2O (SV10). Mean SV10 was 1.16 +/- 0.06 ml in controls but averaged only 0.93 +/- 0.05 in CM (P less than 0.02). Hypercapnia caused significantly greater depression of VF in CM than in controls. NE dose-response curves demonstrated increases in both LV dP/dtmax and SV10 in each group. The percent increase in LV dP/dtmax was markedly attenuated n CM, but the increments in SV10 did not differ. The mean histological score in the CM animals was 1.6 +/- 0.1, indicating extensive myofiber injury. No histological abnormalities were observed in the controls. Thus functional defects correlated with the presence of histopathological changes. In addition, a dissociation of velocity (dP/dtmax) and force (SV10) responsiveness to inotropic stimulation was identified in the CM group.

Animals↗

PubMed1982

Myocardial responses to alpha-adrenoceptor stimulation with methoxamine hydrochloride in lambs.

This study was undertaken to evaluate the effects of methoxamine on left ventricular performance, coronary blood flow (CBF), and myocardial oxygen consumption (MVO2) in lambs. Measurement of maximum rate of rise of left ventricular pressure (LV dP/dtmax), left ventricular end-diastolic pressure (LVEDP), CBF, and MVO2 were made in nine lambs using a hemodynamically controlled preparation. The lambs were given atropine sulfate (1 mg), tetraethylammonium chloride (100 mg), and practolol (4 mg/kg) to provide parasympathetic, ganglionic, and beta-adrenergic blockades. Aortic pressure and blood flow and heart rate were held constant in each lamb. Dose-related increases in LV dP/dtmax and decreases in LVEDP were observed after progressively larger doses of methoxamine ranging from 0.4 to 6.0 mg/kg were given. These positive inotropic responses were eliminated by giving phentolamine (2 mg/kg). CBF, myocardial O2 extraction, and MVO2 did not change significantly. A positive inotropic action of methoxamine was also demonstrated in five additional animals by obtaining ventricular function curves. Initially the mean stroke volume at LVEDP 10 cmH2O (SV10) was 4.11 +/- 0.16 (SE) ml. This value increased to 5.09 +/- 0.28 ml after methoxamine (P less than 0.01). After phentolamine, SV 10 fell to 4.37 +/- 0.08 ml (P less than 0.05). These observations support the hypothesis that alpha-adrenergic receptors are present and mediate a substantial positive inotropic action on neonatal lamb myocardium.

Animals↗

PubMed1982

Coronary dilator actions of adenosine and CO2 in experimental diabetes.

We have previously shown that coronary regulation is altered in the diabetic lamb. In the present investigation the effects of hypercapnic acidosis (increases CO2) and adenosine on coronary sinus flow (CF; ml . min-1 . 100 g-1 LV) were assessed in 13 controls and 7 diabetic lambs (glucose 1,084 +/- 193 mg/dl) given alloxan (150 mg/kg) 2 days prior to study. All measurements were made under conditions of constant aortic pressures and cardiac output. Left ventricular (LV) performance was continuously recorded; O2 content, O2 and CO2 partial pressure, pH, and glucose concentrations were compared in simultaneous sinus and arterial samples. Dose-response curves (0.30 micrograms . min-1 . kg-1) indicated a linear relationship between adenosine and CF. At infusion rates of 30 (iv) or 3 (LV) micrograms . min-1 . kg-1 adenosine increased CF by 30 and 21 ml . min-1 . 100 g-1 LV, respectively in control (P less than 0.001) but not in diabetic lambs. With increases CO2 (80 mmHg; pH 6.95), CF increased substantially (control 60 ml; diabetic 45 ml) in both groups (P less than 0.001). The dilator action of adenosine was enhanced in control during increases CO2, and significant responses to adenosine appeared in the diabetic group. It is concluded that increases [H+] has a potent direct coronary dilator action in both control and diabetic lambs and enhances responsiveness to adenosine. Sensitivity to adenosine is reduced in diabetics, and this subsensitivity is largely reversed by hypercapnic acidosis.

Acidosis, Respiratory↗

PubMed1981

Inotropic responsiveness of the heart in catecholamine cardiomyopathy.

Inotropic responsiveness to norepinephrine (NE) or Ca2+ was studied in 15 rabbits with catecholamine cardiomyopathy (CM) and the results were compared with 11 controls. The former group was prepared by infusing NE (2 micrograms/min/kg) for 90 minutes, 2 to 3 days prior to study, and injury was confirmed and quantified histologically. Comparison of NE dose-response curves relating percent increase of left ventricular (LV) dP/dt max to NE dose in six controls and 10 CM hearts revealed significant depression of CM contractility. Responses to graded infusions of Ca2+ were also determined in five controls and in five CM animals. With the increases in serum Ca2+ identical in the two groups, the percent increases in dP/dt max were less in CM hearts. Further, NE dose-response curves obtained during continuous CaCl2 infusion were sharply attenuated in CM hearts and initial LV end-diastolic pressure (LVEDP) in the CM hearts was considerably higher than in the controls. It is concluded that inotropic sensitivity to NE is reduced in CM hearts. This cannot be ascribed to altered beta-receptors alone, because responsiveness to Ca2+ was also reduced. Myocardial damage was indicated by histology and elevated LVEDP. Moreover, the normalized percent data suggest tht the remaining viable fibers in the CM hearts were functioning subnormally and thus reduced performance was not due solely to the decreased number of contracting units.

Animals↗

PubMed1981

Effects of insulin on ventricular function in diabetic lambs with acidosis.

Diabetes mellitus (DM) was induced in 10 lambs by giving alloxan (150 mg/kg). Two to 4 days later, mean values for glucose were 748 mg/dl, and for arterial pH 7.25 (acute group). Two additional lambs were studied after 3 mo of DM (chronic group). Data were compared with 7 controls (glucose 128 mg/dl, pH 7.36). Left ventricular (LV) performance was assessed from function curves and measurements of LV dP/dtmax. Stroke volume ejected at LV end-diastolic pressure of 5 cmH2O (SV5) was calculated from regression analysis of each curve. SV5 averaged 2.83 +/- 0.34 ml in controls and 2.90 +/- 0.23 ml in the acute diabetics (not significant). Mean values for LV dP/dtmax also did not differ. A significant correlation was found between SV5 and LV weight (P less than 0.001). SV5 was normalized as ml/100 g LV, and average values for the three groups were identical. Insulin (10 U/kg) caused a progressive fall in SV5 in diabetics with severe acidosis (pH 7.00), but not in those with less acidosis (pH 7.28). In nondiabetics given lactic acid (pH 7.01), SV5 fell to 60% of initial values 1 h after insulin. Acidemic animals not given insulin showed no reduction in LV performance in the same time interval. Adrenergic support is necessary to prevent cardiac failure associated with acidosis. The present findings are ascribed to inhibition by insulin of catecholamine inotropic action on myocardium.

Animals↗

PubMed1981

Negative inotropic effects of phenol on isolated cardiac muscle.

Phenol appears in high concentrations in renal failure with uremia. The effects of this material on contractile activity of isolated cardiac muscle were studied in right ventricular moderator band (MB) of piglets and papillary muscle (PM) of cats and kittens. The muscles were bathed in modified Krebs solution containing 5.6 mM glucose at 30 C and gassed with 95% O2 and 5% CO2. They were paced at 24 contractions per minute, isometrically at Lmax. Over the range 2.5-119.0 mg%, phenol produced dose-related decreases in both developed tension (DT) and maximal rate of tension development (max dT/dt) in MB of piglets. In contrast, the dose-dependent negative inotropic effect of phenol was not detected in feline PM until concentrations in excess of 12.5 mg% were used. Increasing extracellular Ca2+ from 2.5 to 5.0 mM as well as the addition of norepinephrine (3.94 x 10(-7) M) attenuated the phenol-induced cardiac depression in porcine MB. There were no further changes in either DT or max dT/dt when the extracellular Ca2+ was increased to 10 mM. These findings demonstrate that phenol elicits a direct negative inotropic effect on mammalian cardiac muscle that is modified by calcium and norepinephrine. Phenol may participate in the biochemical alterations leading to cardiac failure and death in uremia.

Animals↗