Biomedical subjects

G R Norton

Publications and source records attributed to G R Norton.

At least 37 records · Page 2Linked to original sources

PubMed1999

Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart.

Presently, the physiological significance of myocardial adenosine A2a receptor stimulation is unclear. In this study, the influence of adenosine A2a receptor activation on A1 receptor-mediated antiadrenergic actions was studied using constant-flow perfused rat hearts and isolated rat ventricular myocytes. In isolated perfused hearts, the selective A2a receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2, 4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) potentiated adenosine-mediated decreases in isoproterenol (Iso; 10(-8) M)-elicited contractile responses (+dP/dtmax) in a dose-dependent manner. The effect of ZM-241385 on adenosine-induced antiadrenergic actions was abolished by the selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10(-7) M), but not the selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS-1191, 10(-7) M). The A2a receptor agonist carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at 10(-5) M attenuated the antiadrenergic effect of the selective A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), whereas CSC did not influence the antiadrenergic action of this agonist. In isolated ventricular myocytes, CSC potentiated the inhibitory action of adenosine on Iso (2 x 10(-7) M)-elicited increases in intracellular Ca2+ concentration ([Ca2+]i) transients but did not influence Iso-induced changes in [Ca2+]i transients in the absence of exogenous adenosine. These results indicate that adenosine A2a receptor antagonists enhance A1-receptor-induced antiadrenergic responses and that A2a receptor agonists attenuate (albeit to a modest degree) the antiadrenergic actions of A1 receptor activation. In conclusion, the data in this study support the notion that an important physiological role of A2a receptors in the normal mammalian myocardium is to reduce A1 receptor-mediated antiadrenergic actions.

Adenosine↗

PubMed1998

Adenosine mediates sustained adrenergic desensitization in the rat heart via activation of protein kinase C.

Adenosine attenuates the myocardial metabolic and contractile responses induced by ss-adrenergic stimulation. Our study was conducted to investigate the longevity of this antiadrenergic action after adenosine exposure. Adenosine (33 micromol/L) was infused into isolated perfused rat hearts for 1, 5, 30, or 60 minutes, and the adrenergic responsiveness (AR) to isoproterenol (10(-8) mol/L) was determined at the end of each infusion period and during a 45-minute adenosine washout period. Interstitial levels of adenosine, as determined from epicardial surface transudates, returned to preinfusion levels within 10 minutes of washout. The duration of adenosine infusion had no effect on the extent of attenuation of AR at the end of the infusion. Whereas AR returned to preadenosine levels with washout of shorter adenosine infusions (1 and 5 minutes), there was a slow and incomplete recovery of AR after the longer exposures (30 and 60 minutes) to adenosine. The magnitude of this persistent antiadrenergic effect (PAE) of adenosine at 15 minutes of washout was proportional to the epicardial concentration of adenosine during infusion of the nucleoside. Infusion of adenosine either with the nonselective adenosine receptor antagonist 8-p-sulfophenyl theophylline or with the selective A1-receptor antagonist 1,3-dipropyl, 8-cyclopentylxanthine, abolished the PAE during the washout period. In addition, the PAE could be demonstrated only with the selective A1-receptor agonist 2-chloro-N6-cyclopentyladenosine and not with the selective A3-receptor agonist 4-aminobenzyl-5'-N methylcarboxamido-adenosine. When the protein kinase C (PKC) inhibitor chelerythrine was coadministered with adenosine, the PAE of adenosine was not apparent during adenosine washout. A 30-minute infusion of phenylephrine, an alpha-adrenergic agonist that enhances PKC activity, produced a PAE that lasted for up to 30 minutes of washout. This effect was prevented by the coinfusion of chelerythrine. Thus, it is concluded that the PAE of adenosine is determined by the myocardial concentration of this nucleoside and is manifested when myocardial concentrations of adenosine returned to baseline levels. Moreover, a 5-minute duration of adenosine exposure is required for the expression of the PAE. This latter effect seems to be dependent on adenosine-induced PKC activation via A1-receptors.

Adenosine↗

PubMed1998

Reduced cardiac stiffness following exercise is associated with preserved myocardial collagen characteristics in the rat.

We determined whether the increment in cardiac end-diastolic compliance (a reduced diastolic stiffness constant) following endurance training is related to alterations in myocardial collagen characteristics. Sixteen weeks of habitual exercise (Ex) in rats, which produced left ventricular (LV) hypertrophy (LVH) [LV weight in g: Ex = 1.01 (0.04), sedentary control = 0.89 (0.04); P < 0.05], resulted in a reduced LV end-diastolic (LVED) chamber stiffness [slope of the linearised LVED pressure versus LVED internal diameter relation in kPa x mm(-1): Ex = 0.67 (0.03), control = 0.80 (0.03); P < 0.05]. The increased LVED chamber distensibility was associated with an attenuated myocardial stiffness [slope of the linearised LVED stress versus strain relation in g x cm(-2); Ex= 15 (3), control = 25 (2); P < 0.05]. Although LV total collagen content (mg) was increased in the exercised rats [Ex = 5.0 (0.3), control = 4.1 (0.2); P < 0.05], this was a reflection of the presence of LVH, as the myocardial collagen concentration (microg x mg(-1) LV wet weight) was unaltered [Ex = 4.9 (0.2), control = 4.6 (0.2)]. Furthermore, habitual exercise did not influence the percentage of myocardial collagen extracted following cyanogen bromide digestion (an index of collagen cross-linking), [i.e. Ex = 38 (3), control = 38 (3)], nor the proportion of myocardial collagen phenotypes I and III [I/III; Ex = 3.04 (0.20), control = 2.85 (0.22)]. In conclusion, exercise-induced increments in end-diastolic myocardial distensibility are unlikely to be a consequence of alterations in the properties of myocardial collagen.

Animals↗

PubMed1998

Novel attributes of an androgenic steroid-mediated increase in cardiac end diastolic stiffness in rats.

Although cardiac early and mid-diastolic stiffness constants are well accepted as being modulated by alterations in myocyte active processes, increments in left ventricular end diastolic (LVED) stiffness (LVED k; g x cm(-2)) in classical pathological models of a reduced LVED k (e.g., diabetes mellitus (DM) and hypertension) are determined largely by the properties of the myocardial extracellular matrix (ECM). As such, increases in LVED k in the latter cardiac pathologies are insensitive to acute changes in cardiac load, heart rate, and contractility. We examined whether the same attributes that apply to changes in LVED k in DM and in spontaneously hypertensive rats (SHRs) also apply to an androgenic steroid (nandrolone decanoate; 5 mg x kg(-1) biweekly) induced increase in LVED k. Myocardial collagen (ECM) characteristics and the capacity of acute verapamil-mediated changes in cardiac dynamics to impact on LVED k were evaluated after 3 months of steroid treatment to rats, 4 months of DM in rats, and in 45-week-old SHRs. Chronic steroid administration increased LVED k (steroid = 42 +/- 4, control = 25 +/- 2; p < 0.01). An acute infusion of verapamil to steroid-treated rats decreased LVED k to values not different from controls (29 +/- 3; p < 0.05 as compared with LVED k at baseline). Measures of myocardial collagen concentrations, phenotype ratios, and cross-linking were unchanged following steroid administration. Verapamil failed to alter the increased LVED k that occurs in either rats with DM or in SHRs, despite similar effects on cardiac dynamics as those noted in steroid-treated rats. The increased LVED k in the former animal models was associated with alterations in the ECM. In conclusion, the unique lack of association of the androgenic steroid-induced increase in LVED k with alterations in the myocardial ECM and the novel sensitivity of the steroid-mediated increment in LVED k to acute alterations in cardiac dynamics further supports the notion that changes in LVED k should not be considered to be a reflection of ECM characteristics in all cardiac conditions.

Androgens↗

PubMed1998

Dimensions of perfectionism, hopelessness, and attempted suicide in a sample of alcoholics.

This study assessed whether specific dimensions of perfectionism and hopelessness were elevated in individuals who had made a serious suicide attempt in comparison to individuals with no history of suicide attempts. A sample of 39 inpatients with alcoholism who had made a serious suicide attempt and a matched sample of 39 inpatients with alcoholism but no history of suicide attempts completed the Multidimensional Perfectionism Scale, the Hopelessness Scale, ratings of achievement and social hopelessness, and the Beck Depression Inventory. The attempter group had higher scores on socially prescribed perfectionism, generalized hopelessness, achievement hopelessness, social hopelessness, and depression. A discriminant function analysis revealed that depression, social hopelessness, socially prescribed perfectionism, and other-oriented perfectionism were unique discriminators of the suicide groups. The results are discussed in terms of the importance of social personality variables in attempted suicide.

Achievement↗

PubMed1997

Myocardial stiffness is attributed to alterations in cross-linked collagen rather than total collagen or phenotypes in spontaneously hypertensive rats.

BACKGROUND: The relative contributions of increases in myocardial collagen, collagen cross-linking, and the ratio of type I to type III collagen to the stiff myocardium in hypertension were determined. METHODS AND RESULTS: We compared the action of hydralazine (0.07 mmol x kg(-1) x d(-1)) with that of captopril (0.22 mmol x kg(-1) x d(-1)) on the left ventricular end-diastolic (LVED) myocardial stiffness constant, k (g x cm(-2)) and LV myocardial interstitial characteristics in spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) control rats. LVED k (SHR, 27.9+/-1; WKY, 19.5+/-1.2; P<.01), myocardial hydroxyproline concentrations (HPRO; microg/mg dry wt) (SHR, 4.19+/-0.16; WKY, 3.17+/-0.09; P<.001), and collagen type I/III ratios (SHR, 7.1+/-0.7; WKY, 2.1+/-0.2; P<.001) were increased, whereas the percentage of myocardial collagen extracted after cyanogen bromide digestion (an index of cross-linked collagen) was decreased (SHR, 17+/-3; WKY, 41+/-4; P<.001) in SHRs compared with WKY controls. Captopril therapy reduced LVED k, myocardial HPRO, collagen type I/III, and augmented collagen solubility (43+/-4) in SHRs to values similar to those measured in WKY controls. Hydralazine therapy, despite a favorable effect on LVED k in SHRs (20.+/-1.6, P<.01 compared with untreated SHRs), failed to influence either myocardial HPRO (4.18+/-0.18) or collagen type I/III (8+/-1) but did improve collagen solubility (31+/-2). CONCLUSIONS: An association between alterations in LVED k and collagen solubility but not between changes in LVED k and total collagen or phenotype ratios after antihypertensive therapy in SHRs suggests that myocardial stiffness in hypertension is the consequence of an enhanced myocardial collagen cross-linking rather than of an increase in total collagen or type I phenotype concentrations.

Animals↗

PubMed1997

Anxiety sensitivity and drug choice in individuals seeking treatment for substance abuse.

Sixty-four men and 49 women who applied for admission to outpatient substance abuse programs provided information on their preferred chemical (e.g., alcohol) and information on their alcohol and other chemical use. They also completed a package of self-report questionnaires including the Anxiety Sensitivity Index (ASI). The results showed that men who scored high on the ASI were more likely than low ASI subjects to prefer depressants, especially alcohol. Subjects who scored low on the ASI were more likely to prefer marijuana. ASI score did not predict chemical preference among women. All female ASI groups (high, medium and low) showed a preference for alcohol. The implications of these findings are discussed.

Adult↗

PubMed1997

Do patients with chronic pain selectively attend to pain-related information?: preliminary evidence for the mediating role of fear.

Preliminary evidence from a study using a modified Stroop paradigm suggests that individuals with chronic pain selectively attend to pain-related information. The current study was conducted in an attempt to replicate and extend this finding. Nineteen patients with chronic pain stemming from musculoskeletal injury and 22 healthy control subjects participated. All participants completed a computerised task designed to evaluate attentional allocation to cues thematically related to pain and injury via measurement of detection latencies for dot-probes that followed their presentation. Results indicated that patients did not differ from control subjects in their pattern of responses to dot-probes that were presented following either the pain- or injury-related cues. This pattern of results continued to hold true after including level of depression as a covariate in the analysis. However, when patients were divided on the basis of scores on the Anxiety Sensitivity Index (Peterson, R.A. and Reiss, S., Anxiety Sensitivity Index Manual, 2nd edn., International Diagnostic Systems, Worthington, OH, 1992), a measure related to fear of pain (Asmundson, G.J.G. and Norton, G.R., Behav. Res. Ther., 34 (1996) 545-554), those with low anxiety sensitivity shifted attention away from stimuli related to pain whereas those with high anxiety sensitivity responded similarly to dot-probes regardless of the parameters of presentation. These results suggest that the operation of the information processing system in patients with chronic pain may be dependent on a patient's trait predisposition to fear pain. Theoretical and ecological implications are discussed.

Adult↗

PubMed1996

Aminoguanidine prevents the decreased myocardial compliance produced by streptozotocin-induced diabetes mellitus in rats.

BACKGROUND: A decreased cardiac compliance is a major feature of the cardiomyopathy of diabetes mellitus. Either an increase in the resistance afterload to the LV or an increase in collagen cross-linking induced by the formation of advanced glycosylation end products (AGEs) of collagen may be responsible for the stiff myocardium. To evaluate these hypotheses, we examined the effect of captopril, an afterload-reducing agent, and aminoguanidine, a nucleophilic hydrazine that prevents the accumulation of collagen AGEs, on left ventricular end-diastolic (LVED) compliance after 4 months of streptozotocin (0.26 mmol/kg)-induced diabetes mellitus in rats. METHODS AND RESULTS: Diabetes mellitus produced a decrease in LV chamber compliance as a result of an increased myocardial stiffness (slope of the linearized LVED stress-LVED strain relation [unitless]: diabetes mellitus, 47+/-4; control, 27+/-3; P<.001) and an increase in blood pressure as a result of an elevated vascular resistance. LV end-systolic elastance was unaltered by diabetes mellitus. The stiff myocardium was not associated with changes in the myocardial collagen volume fraction or total hydroxyproline concentration but was associated with an increased myocardial collagen fluorescence (fluorescence units/microg hydroxyproline) (diabetes mellitus, 11+/-1.1; control, 6.6+/-0.7; P<.01). Captopril therapy (0.22 mmol x kg(-1) x d(-1)), despite producing a decrease in blood pressure through alterations in vascular resistance, failed to decrease myocardial stiffness in rats with diabetes mellitus. Alternatively, administration of aminoguanidine (7.35 mmol x kg(-1) x d(-1)) prevented both the enhanced myocardial collagen fluorescence (7.1+/-1.2) and the increased slope of the linearized LVED stress-LVED strain relation (29+/-2) but did not change markers of blood glucose control. CONCLUSIONS: These results demonstrate that diabetes mellitus can produce a stiff myocardium before the development of myocardial fibrosis. The stiff myocardium in the early stages of the development of the cardiomyopathy of diabetes mellitus is not a consequence of an increase in ventricular resistance afterload and in these circumstances is associated with the formation of collagen AGEs.

Animals↗

PubMed1996

Renal effects of a high unsaturated fat diet in renal artery stenosis in rats.

The renal effects of an unsaturated fat (UNSAT) diet in mild to moderate two-kidney, one-clip (2K1C) renovascular hypertension were evaluated. An UNSAT diet (37% by energy) prevented the development of hypertension compared to 2K1C rats fed a high saturated fat (SAT) (37% by energy) and a normal fat (CONTROL) (11% by energy) diet. Urinary sodium and fractional sodium excretion increased in 2K1C rats as compared to SHAM operated controls, regardless of the diet received. In the early weeks of the experiment (weeks 2-4 post-surgery to induce hypertension), an enhanced natriuresis occurred in the 2K1C UNSAT as compared to the 2K1C CONTROL and SAT diet groups. This resulted from an increase in the glomerular filtration rate (GFR in mls.min-1) as measured using the single-injection [51Cr] EDTA method (2K1C UNSAT; 1.99 +/- 0.18 versus 2K1C SAT; 1.27 +/- 0.09, p < 0.02; and versus SHAM CONTROL; 1.45 x 0.01; p < 0.02). The increased GFR was not associated with alterations in effective renal plasma flow (ERPF) as measured using the single-injection [125I] Na hippurate method. No differences in sodium excretion; GFR; ERPF or renal blood flow (microsphere technique) were noted between the 2K1C UNSAT and SAT diet groups at weeks 6-8 post-surgery, despite a continued antihypertensive effect of the UNSAT diet. Hence, the antihypertensive effect of an unsaturated fat diet in 2K1C renovascular hypertension in rats is associated with transient glomerular changes leading to an enhanced natriuresis.

Animals↗

PubMed1996

Social, blood/injury, and agoraphobic fears in patients with physically unexplained chronic pain: are they clinically significant?

Recently, there has been increased interest in the extent to which chronic pain patients fear and avoid activities that are thought to be related to the experience of pain. To date, however, few studies have evaluated the nature and extent of nonpain fears in these patients. The purpose of the present study was to address this paucity. The Fear Questionnaire was administered to 130 patients with physically unexplained chronic pain and 93 patients with a chronic condition unrelated to pain. Results indicated that the chronic pain patients were more fearful and avoidant of social interactions/situations and blood/injury than were the patient controls. Agoraphobia was minimal and did not differ significantly between groups. As well, the proportions of chronic pain patients indicating definite avoidance of particular situations related to blood/injury phobia (i.e., injection/minor surgery, hospitals, sight of blood, and thoughts of injury/illness) and social phobia (i.e., being watched/stared at, and speaking/acting to an audience) were significantly greater when compared to the patient controls. These results indicate that nonpain fear and avoidance are common in patients with chronic pain. Implications regarding the significance of these fears and avoidance behaviours on the experience and maintenance of pain symptoms and related disability are discussed.

Adolescent↗

PubMed1996

Panic disorder or social phobia: which is worse?

Twenty-eight patients with panic disorder (PD) and 30 with social phobia (SP) were compared on demographic and psychopathology measures. The demographic comparisons showed that, although people with SP were better educated, they were more likely to be single, living alone, and unemployed. The comparisons of psychopathology showed that the proportion of people with PD and SP with a life time major affective disorder did not differ, nor did the two groups differ on the proportion of Ss reporting past suicide attempts. However, a greater proportion of patients with SP had Brief Michigan Alcohol Screening Test scores above 5, indicating alcohol abuse problems. The implications of these findings are discussed.

Activities of Daily Living↗

PubMed1996

Association between HIV distal symmetric polyneuropathy and Mycobacterium avium complex infection.

OBJECTIVES: Pronounced infiltration of activated macrophages occurs in the peripheral nerves of patients with HIV distal symmetric polyneuropathy (DSPN). Mycobacterium avium complex (MAC) is a common facultative intracellular parasite of the macrophage in advanced HIV disease and may induce macrophage activation. Whether MAC disease is associated with DSPN was examined prospectively. METHODS: One hundred and fifty consecutive patients with HIV infection were assessed for the probability of DSPN. Blood cultures for MAC were performed, independently of neurological assessment, as part of the investigation of unexplained fever, anaemia, weight loss, or, less commonly, diarrhoea. RESULTS: There were 20 patients with possible, 14 with probable, and 22 with definite HIV DSPN. Blood cultures for MAC were performed on 80 patients, of whom 39 were positive and 41 negative. The test for trend, when corrected for CD4 count, disclosed a significant association (P = 0.01). There was no statistically significant association between DSPN and cytomegalovirus (CMV) disease. CONCLUSION: Coinfection of the macrophage by MAC may further activate the HIV infected macrophage thereby accelerating the elaboration of neural toxins or MAC infection of the macrophage itself may lead to the production of neural toxins.

Adult↗

PubMed1996

Habitual exercise attenuates myocardial stiffness in diabetes mellitus in rats.

The effects of regular voluntary (habitual) exercise on left ventricular (LV) diastolic performance, as well as on those hemodynamic, LV geometric and myocardial interstitial changes that influence myocardial diastolic function, were examined in streptozocin (50 mg/kg)-induced diabetes mellitus (DM) in male rats. After 16 wk of regular exercise on voluntary running wheels, cardiac performance was measured in anesthetized open-chest ventilated rats. Rats with DM developed a decrease in LV end diastolic (LVED) chamber and myocardial wall compliance associated with an increase in myocardial collagen fluorescence (a measure of collagen advanced glycosylation end product concentrations), an increase in systemic blood pressure, and a dilated LV. However, LV end-systolic elastance and total myocardial hydroxyproline concentration were unchanged. Habitual exercise prevented the augmented LVED chamber stiffness (slope of linearized LVED pressure-strain relation, DM vs. exercise DM, P < 0.01) and myocardial wall stiffness (slope of linearized LVED stress-strain relation, DM vs. exercise DM, P < 0.001) produced by DM. However, neither markers of blood glucose control, blood pressure, LV geometry, myocardial hydroxyproline concentration, nor collagen fluorescence were altered by the exercise program. A reduced LVED chamber and myocardial wall stiffness, as noted in euglycemic control rats in response to regular exercise, was also not associated with hemodynamic or myocardial interstitial alterations. Therefore, regular voluntary exercise opposes the decrement in myocardial diastolic performance produced by DM in male rats without influencing the accumulation of myocardial advanced glycosylation end products thought to be partly responsible for the stiff myocardium after chronic hyperglycemia. The beneficial effects of regular exercise on myocardial compliance are likely to be a consequence of changes in active as opposed to passive properties of the myocardial wall.

Animals↗

PubMed1995

Preload recruitable stroke work in the presence of intact cardiovascular reflexes in rats fed a diet high in unsaturated fats.

A decreased inotropic effect of myocardial beta receptor agonists in animals receiving diets high in unsaturated fats (UNSAT) has been demonstrated. The effect of an UNSAT diet on myocardial systolic performance under different loading conditions, in the presence of intact cardiovascular reflexes, has not been examined. We investigated the effect of an UNSAT diet on preload recruitable stroke work (SW) in the anaesthetised, open chest, ventilated rat. A control (CONTROL, 11% by energy), a high saturated fat (SAT, 37% by energy) and a high UNSAT (37% by energy) diet were fed to three groups of rats. At three months, systolic myocardial performance (stroke work: SW) at increasing left ventricular end diastolic pressures (LVEDP) was measured within a physiological preload range. There were no significant differences in either the slope or the intercept of the LVEDP/SW relation were found between the three diet groups. Systemic vascular resistance and heart rate decreased to the same extent in the three diet groups over the range of preloads examined. This occurred as a consequence of intact baroreceptor reflexes. Hence dietary modulation of unsaturated fats does not influence myocardial contraction over a wide range of physiological preloads in the presence of intact baroreceptor reflexes.

Animals↗

PubMed1995

Anxiety sensitivity in patients with physically unexplained chronic back pain: a preliminary report.

It has been proposed that high anxiety sensitivity amplifies a number of fears and anxiety reactions. The purpose of this study was to examine whether anxiety sensitivity influences pain-related anxiety and associated cognitive and affective reactions in patients with physically unexplained chronic back pain. Seventy patients with chronic back pain without demonstrable organic pathology completed a battery of questionnaires prior to admission to a multidisciplinary treatment centre. Fourteen patients (20.0%) were classified as high, 44 (62.9%) as medium and 12 (17.1%) as low anxiety sensitive. Multivariate analysis of variance indicated that the high anxiety sensitive patients were more negatively affected by their experience with pain. Specifically, high anxiety sensitivity patients exhibited greater cognitive disruption and anxiety in response to pain, greater fear of negative consequences of pain, and greater negativity of affect than the other groups. Groups did not differ in the intensity of pain that they were experiencing. The proportion of high anxiety sensitive patients reporting current use of analgesic medication was, however, significantly greater than the medium and low anxiety sensitive patients. Correlational analyses indicated significant associations between anxiety sensitivity and pain-related cognitive/affective variables that were independent of pain severity. These results suggest that chronic back pain patients with high anxiety sensitivity, despite equal levels of pain severity, are more likely to be negatively affected by their pain experiences than those with medium and low anxiety sensitivity.

Adolescent↗

PubMed1995

An androgenic steroid decreases left ventricular compliance in rats.

The effect of chronic administration of an androgenic steroid on left ventricular (LV) compliance and contractility was studied in rats. Rats received a biweekly intramuscular injection of nandrolone decanoate (5 mg/kg; steroid group) or the vehicle (control group) for 3 mo. Cardiac performance was measured in anesthetized open-chest ventilated rats. LV compliance was determined from the slope of the LV end-diastolic pressure (LVEDP) vs. LV end-diastolic (LVED) strain relation measured in the long and short axes of the LV. LV regional myocardial compliance was determined from the slope of the LVED stress vs. LVED strain relation (myocardial elastic stiffness constant). Cardiac contractility was determined from the slope of the LV end-systolic (LVES) pressure vs. LVES strain relation. Systolic performance was also assessed from the slope of the pressure-length area (PL area) or stroke work vs. LVED strain and LVEDP relations. Nandrolone decanoate decreased body weight, heart weight, and plasma testosterone concentrations but increased the heart weight-to-body weight ratio. Nandrolone decanoate decreased LV compliance (slope of LVEDP vs. LVED strain relation in long and short axes; steroid vs. control, P < 0.01). This occurred as a result of an increased regional myocardial stiffness (myocardial elastic stiffness constant; steroid vs. control, P < 0.01), which resulted in a reduced cardiac systolic performance (PL area vs. LVEDP, slope of steroid vs. control group, P < 0.005). Diastolic geometry (LV wall thickness-to-radius ratio) and cardiac contractility were unchanged with steroid administration. In conclusion, chronic administration of the androgenic steroid nandrolone decanoate decreases LV myocardial compliance and thus overall cardiac performance without altering contractility in rats.

Anabolic Agents↗

PubMed1995

Exercise-induced cardiac hypertrophy is associated with an increased myocardial compliance.

Left ventricular (LV) chamber and myocardial wall compliance were investigated in rats with exercise-induced cardiac hypertrophy. Voluntary exercise training was performed on running wheels. After 16 wk of exercise training, cardiac performance was measured in anesthetized open-chest ventilated rats. LV end-diastolic performance was calculated from both short-axis external diameter and long-axis segmental length measurements. Exercise-trained rats developed significant LV hypertrophy (1.03 +/- 0.02 g) compared with control rats (0.91 +/- 0.03 g; P < 0.01). The physiological hypertrophy was associated with an increased LV wall thickness-to-internal radius ratio consistent with a concentric geometry. LV end-diastolic stiffness (slope of the linearized LV end-diastolic pressure-strain relationship) was decreased in both the short (P < 0.02) and long (P < 0.02) axis of LV as a result of exercise training. The LV end-diastolic chamber stiffness (slope of the linearized LV end-diastolic pressure-volume relationship) was also decreased in the exercised group (P < 0.05). The decreased chamber stiffness occurred as a consequence of a decrease in the regional myocardial wall elastic stiffness (slope of the linearized LV end-diastolic stress-strain relationship; P < 0.05). Thus an increased LV wall thickness as a result of exercise-induced LV hypertrophy is associated with an enhanced ventricular chamber compliance, which in turn is attributed to a decrease in the diastolic stiffness of the myocardial wall.

Animals↗