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Biomedical subjects

A M Feldman

Publications and source records attributed to A M Feldman.

At least 91 records · Page 5Linked to original sources
PubMed1994

Ventricular systolic assessment in patients with dilated cardiomyopathy by preload-adjusted maximal power. Validation and noninvasive application.

BACKGROUND: Noninvasive cardiac-specific analysis of contractile function in patients with dilated heart failure remains problematic. This study tests whether maximal power divided by the square of end-diastolic volume (PWRmx/EDV2, or preload-adjusted PWRmx) can provide such assessment. METHODS AND RESULTS: To validate the load insensitivity of the PWRmx index and determine its response to contractile change, 24 subjects with chronic dilated cardiomyopathy underwent invasive pressure-volume catheterization study using the conductance catheter technique. Preload was transiently reduced by 30% using balloon occlusion of the inferior vena cava, and afterload impedance was lowered by 50%, induced by a bolus injection of nitroglycerin. Contractile state was varied by intravenous dobutamine, verapamil, or esmolol. PWRmx was calculated from the simultaneous product of ventricular pressure and rate of volume change (dV/dt), the latter derived from the volume catheter signal. PWRmx varied directly with preload but was minimally influenced by afterload. However, PWRmx/EDV2 was not significantly altered by either loading change. PWRmx/EDV2 did vary with contractility, correlating closely with changes in the end-systolic pressure-volume relation (r = .91, P < .001). To test the noninvasive application of this index, 12 additional patients were studied, with PWRmx/EDV2 derived from nuclear ventriculography combined with a novel method to measure central arterial pressures. Subjects received intravenous nitroprusside or dobutamine in random order. Ejection fraction increased similarly with both agents (+42.9 +/- 8.9% for dobutamine and +29.4 +/- 5.3% for nitroprusside, both P < .01). In contrast, PWRmx/EDV2 did not significantly change with nitroprusside but increased by 126 +/- 16.1% with dobutamine (P < .01). CONCLUSIONS: Preload-adjusted PWRmx is a steady-state index of ventricular systolic function that is sensitive to inotropic state and minimally influenced by physiological changes in afterload impedance or volume load. It appears useful for noninvasive cardiac-specific analysis of acute drug effects.

Cardiac Catheterization↗
PubMed1994

Age-related changes in beta-adrenergic neuroeffector systems in the human heart.

BACKGROUND: Aging decreases cardiac beta-adrenergic responsiveness in model systems and in humans in vivo. The purpose of this study was to comprehensively evaluate the age-related changes in the beta-receptor-G protein-adenylyl cyclase complex in nonfailing human hearts. METHODS AND RESULTS: Twenty-six nonfailing explanted human hearts aged 1 to 71 years were obtained from organ donors and subjected to pharmacological investigation of beta-adrenergic neuroeffector systems. When the population was subdivided into the 13 youngest and 13 oldest subjects, total beta-receptor density assessed by maximum [125I]ICYP binding (beta max) was reduced in older hearts by 37% in left ventricles and 31% in right ventricles (both P < .05), and the downregulation was confined to the beta 1 subtype (r = .78 left ventricle beta 1 density versus donor age). Older donor hearts exhibited a 3- to 4-fold rightward shift of ICYP-isoproterenol (ISO) competition curves and demonstrated 43% fewer receptors in a high-affinity agonist binding state (P < .05). Older hearts exhibited decreased adenylyl cyclase stimulation by ISO, by zinterol (beta 2-agonist), and by the G protein-sensitive probes forskolin, Gpp(NH)p, and NaF. In contrast, there was no change in response to manganese, a specific activator of the adenylyl cyclase catalytic subunit. Toxin-catalyzed ADP ribosylation in membranes prepared from older versus younger hearts revealed a 29% to 30% reduction (P < .05) with cholera toxin (Gs) but no difference with pertussis toxin (Gi). The systolic contractile response of isolated right ventricular trabeculae to ISO was decreased by 46%, with a 10-fold increase in ISO EC50 in older relative to younger donor hearts. CONCLUSIONS: There is a profound decrease in cardiac beta-adrenergic responsiveness with aging. This occurs by multiple mechanisms including downregulation and decreased agonist binding of beta 1-receptors, uncoupling of beta 2-receptors, and abnormal G protein-mediated signal transduction.

Adenylyl Cyclases↗
PubMed1994

Sudden cardiac death in heart failure. The role of abnormal repolarization.

Congestive heart failure is a common, highly lethal cardiovascular disorder claiming over 200,000 lives a year in the United States alone. Some 50% of the deaths in heart failure patients are sudden, and most of these are probably the result of ventricular tachyarrhythmias. Methods designed to identify patients at risk have been remarkably unrewarding, as have attempts to intervene and prevent sudden death in these patients. The failure to impact favorably on the incidence of sudden death in heart failure patients stems largely from a lack of understanding of the underlying mechanisms of arrhythmogenesis. This article explores the role of abnormalities of ventricular repolarization in heart failure patients. We will examine evidence for the hypothesis that alteration of repolarizing K+ channel expression in failing myocardium predisposes to abnormalities in repolarization that are arrhythmogenic. The possible utility of novel electrophysiological and ECG measures of altered ventricular repolarization will be explored. Understanding the mechanism of sudden death in heart failure may lead to effective therapy and more accurate identification of patients at greatest risk.

Action Potentials↗
PubMed1994

Endomyocardial gene expression during development of pacing tachycardia-induced heart failure in the dog.

Selective and specific changes in gene expression characterize the end-stage failing heart. However, the pattern and relation of these changes to evolving systolic and diastolic dysfunction during development of heart failure remains undefined. In the present study, we assessed steady-state levels of mRNAs encoding a group of cardiac proteins during the early development of left ventricular dysfunction in dogs with pacing-induced cardiomyopathy. Corresponding hemodynamic assessments were made in the conscious state in the same animals and at the same time points at baseline, after 1 week of ventricular pacing, and at the onset of clinical heart failure. Systolic dysfunction dominated after 1 week of pacing, whereas diastolic dysfunction was far more pronounced with the onset of heart failure. Atrial natriuretic factor mRNA was undetectable in 7 of 12 hearts at baseline but was expressed in all hearts at 1 week (P < .01 by chi 2 test), and it increased markedly with progression to failure (P = .05). Creatine kinase-B mRNA also rose markedly with heart failure (P < .01). Levels of mRNA encoding beta-myosin heavy chain, mitochondrial creatine kinase, phospholamban, and sarcoplasmic reticulum Ca(2+)-ATPase did not significantly change from baseline, despite development of heart failure. Additional analysis to determine if these mRNA changes were related to the severity of diastolic or systolic dysfunction revealed that phospholamban mRNA decreased in hearts with larger net increases in end-diastolic pressure (+19.2 +/- 1.9 mm Hg) compared with those hearts in which it did not change (+4.0 +/- 4.9, P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Effects of vesnarinone on morbidity and mortality in patients with heart failure. Vesnarinone Study Group.

BACKGROUND: Inotropic therapy, other than with digitalis glycosides, has had limited success in patients with chronic congestive heart failure. We investigated whether vesnarinone, a new positive inotropic agent, reduces morbidity and mortality and improves the quality of life of patients with symptomatic heart failure. METHODS: Patients receiving concomitant therapy with digoxin (87 percent) and an angiotensin-converting-enzyme inhibitor (90 percent) who had ejection fractions of 30 percent or less were randomly assigned to receive double-blinded therapy with 60 mg of vesnarinone per day, 120 mg of vesnarinone per day, or placebo. Afer 253 patients had been enrolled, randomization to the 120-mg vesnarinone group had to be stopped because of a significant increase in early mortality in this group. Thereafter, patients were randomly assigned only to 60 mg of vesnarinone per day (a total of 239 patients) or placebo (a total of 238 patients). RESULTS: Significantly fewer patients in the group receiving 60 mg of vesnarinone than in the group receiving placebo (26 vs. 50 patients; P = 0.003) died or had worsening heart failure during the six-month study period. The reduction in risk was 50 percent (95 percent confidence interval, 20 to 69 percent). Similarly, there was a 62 percent reduction (95 percent confidence interval, 28 to 80 percent) in the risk of dying from any cause among the patients receiving vesnarinone. Furthermore, quality of life improved to a greater extent in the vesnarinone group than in the placebo group over 12 weeks (P = 0.008). The principal side effect associated with vesnarinone was reversible neutropenia, which occurred in 2.5 percent of the patients. CONCLUSIONS: Six months of therapy with 60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of vesnarinone are unknown.

Adult↗
PubMed1993

Classification of positive inotropic agents.

Although there is increasing recognition that all inotropic agents are not alike, they continue to be viewed in the generic sense because of the lack of a classification system. Analogous to the classification system proposed for the antiarrhythmic agents over 20 years ago, a classification system is proposed that categorizes inotropic agents according to their mechanisms of action. Agents are classified as those that augment contractility by increasing intracellular levels of cyclic adenosine monophosphate (class I); affect ion channels or pumps (class II); modulate intracellular calcium regulation (class III), and augment contractility through multiple pathways (class IV). This classification system does not suggest that some classes of inotropic agents might be more effective than others nor does it imply that potential beneficial effects are shared by all members of each class of drugs. However, it provides a framework for better understanding of the potential benefits and limitations of the traditional inotropic agents as well as the increasing number of new investigational drugs.

Calcium↗
PubMed1993

Up-regulation of beta 2-adrenergic receptors in previously transplanted, denervated nonfailing human hearts.

OBJECTIVES: The purpose of this study was to examine beta-adrenergic receptor signal transduction in denervated, previously transplanted human ventricular myocardium. BACKGROUND: In model systems, surgical denervation typically results in both presynaptic and postsynaptic supersensitivity in beta-adrenergic receptor pathways and alteration in G protein-mediated signal transduction. METHODS: We examined beta-adrenergic receptor signal transduction in the left and right ventricles removed from nine subjects with a previous transplant and surgical denervation 25 +/- 4 months after their first transplantation. Twenty-six hearts removed from organ donors served as control hearts. RESULTS: Total beta-adrenergic receptor density and stimulation of muscle contraction in isolated right ventricular trabeculae by the nonselective agonist isoproterenol were similar in the transplant and donor groups. Beta 1-receptor density was not different in the left ventricles of the two groups but tended to be reduced (by 29%, p = 0.09) in transplant right ventricles. By contrast, beta 2-receptor density was higher in transplant left and right ventricles relative to the respective values in donor ventricles by 33% in left ventricles and 97% in right ventricles (both p < 0.05). Isoproterenol, which in particulate fractions of human heart stimulates adenylyl cyclase primarily via beta 2-receptors, produced a greater increase in cyclic adenosine monophosphate generation in membranes prepared from transplant left ventricles and right ventricles compared with donors. In contrast, guanosine 5'-[beta,gamma-imido]triphosphate, sodium fluoride and forskolin, which stimulate adenylyl cyclase through nonreceptor/G protein-sensitive mechanisms, yielded similar degrees of adenylyl cyclase stimulation in the two groups, and both pertussis toxin- and cholera toxin-catalyzed adenosine diphosphate ribosylation were not altered in transplanted left ventricles. CONCLUSIONS: These data indicate that the transplanted human heart exhibits an up-regulation of functional beta 2-adrenergic receptors.

Adenylyl Cyclases↗
PubMed1993

Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding.

Left ventricular hypertrophy (LVH) is associated with reinduction of the fetal program of gene expression. It is unclear whether this pattern of cardiac gene expression changes with the development of left ventricular decompensation and failure. To answer these questions, we quantified steady-state levels of mRNA by the polymerase chain reaction in the left ventricular myocardium of rats 8 and 20 weeks after ascending aortic banding. Clinical and hemodynamic assessment identified two distinct groups of animals 20 weeks after aortic banding. The first group (20-week nonfailed LVH) demonstrated substantial LVH but no depression in systolic developed pressure per gram left ventricular weight compared with the age-matched control group. In contrast, a second group of rats exhibited clinical signs of congestive failure as well as a marked diminution in left ventricular developed pressure per gram. Assessment of the levels of mRNA encoding a panel of cardiac proteins demonstrated a greater than twofold increase in beta-myosin heavy chain mRNA and an approximately sixfold increase in atrial natriuretic factor mRNA in left ventricular myocardium of all three groups (8-week LVH, 20-week nonfailed LVH, 20-week failed LVH) when compared with appropriate age-matched control groups. In contrast, Ca(2+)-ATPase mRNA levels were decreased by 50% only in the left ventricular myocardium of animals with both clinical signs and hemodynamic indexes consistent with cardiac decompensation (20-week failed LVH). These results suggest that in rats with ascending aortic banding the hypertrophic phenotype is associated with a selective reinduction of the fetal gene program, which persists even after the development of left ventricular failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Reduced beta 1 receptor messenger RNA abundance in the failing human heart.

Heart failure in humans is characterized by alterations in myocardial adrenergic signal transduction, the most prominent of which is down-regulation of beta 1-adrenergic receptors. We tested the hypothesis that down-regulation of beta 1-adrenergic receptors in the failing human heart is related to decreased steady-state levels of beta 1 receptor mRNA. Due to the extremely low abundance of beta 1 receptor mRNA, measurements were possible only by quantitative polymerase chain reaction (QPCR) or by RNase protection methods. Because the beta 1 receptor gene is intronless and beta 1 receptor mRNA abundance is low, QPCR yielded genomic amplification in total RNA, and mRNA measurements had to be performed in poly (A)(+)-enriched RNA. By QPCR the concentration of beta 1 receptor mRNA varied from 0.34 to 7.8 x 10(7) molecules/microgram poly(A)(+)-enriched RNA, and the assay was sensitive to 16.7 zeptomol. Using 100-mg aliquots of left ventricular myocardium obtained from organ donors (nonfailing ventricles, n = 12) or heart transplant recipients (failing ventricles, n = 13), the respective beta 1 mRNA levels measured by QPCR were 4.2 +/- 0.7 x 10(7)/micrograms vs. 2.10 +/- 0.3 x 10(7)/micrograms (P = 0.006). In these same nonfailing and failing left ventricles the respective beta 1-adrenergic receptor densities were 67.9 +/- 6.9 fmol/mg vs. 29.6 +/- 3.5 fmol/mg (P = 0.0001). Decreased mRNA abundance in the failing ventricles was confirmed by RNase protection assays in total RNA, which also demonstrated a 50% reduction in beta 1 message abundance. We conclude that down-regulation of beta 1 receptor mRNA contributes to down-regulation of beta 1 adrenergic receptors in the failing human heart.

Antisense Elements (Genetics)↗
PubMed1993

Modulation of adrenergic receptors and G-transduction proteins in failing human ventricular myocardium.

During times of physiological stress, the human heart is able to markedly increase contractility. This response is facilitated by the release of norepinephrine from postganglionic sympathetic nerves and epinephrine from the adrenal gland. These neurotransmitters effect a contractile response by interacting with a transmembrane signaling system within the myocyte sarcolemma consisting of beta 1- and beta 2-adrenergic receptors, the guanine nucleotide-binding regulatory proteins Gs and Gi, and the effector enzyme adenylyl cyclase. Activation of this beta-receptor-G-protein-adenylyl cyclase signal transduction complex results in production of the second messenger, cAMP, activation of protein kinase A, and phosphorylation of a group of cellular proteins that are important in excitation-contraction coupling. In contrast to normal human myocardium, the failing human heart is insensitive to adrenergic stimulation. This insensitivity is a result of alterations in the function of this signal transduction pathway, including selective downregulation of the beta 1-adrenergic receptor, uncoupling of beta 2-adrenergic receptors from adenylyl cyclase, and an increase in the functional activity of the inhibitory G-protein. Subtle yet important differences exist between beta-adrenergic neuroeffector mechanisms in idiopathic dilated cardiomyopathy and cardiomyopathy secondary to ischemic heart disease. Most notably, beta-receptors are downregulated to a lesser degree in patients with ischemic heart disease. Therefore, various types of end-stage heart muscle disease may exhibit important pathophysiological differences despite common clinical features and an understanding of the regulatory mechanisms that modulate cardiac signal transduction may have therapeutic implications.

Cardiac Output, Low↗
PubMed1992

Identification of a highly conserved region at the 5' flank of the phospholamban gene.

Phospholamban is a protein that regulates the activity of the sarcoplasmic reticulum Ca(2+)-ATPase. The rat phospholamban gene contains a single intron of 6.5 kilobases which interrupts the 5' untranslated region. Primer extension and nuclease mapping analysis identified a major transcription initiation site 87 nucleotides upstream of the first exon/intron junction. A highly conserved region was identified at the 5' flank of the phospholamban gene. This region contained a TATA motif at position -52 which bound nuclear extract, and a consensus CAAT motif at position -76. This highly conserved region may be important in the regulation of basal transcriptional activity.

Animals↗
PubMed1992

Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.

Thyroid hormone effects on myocardial gene expression have been well defined in animal models, but their relationship to the pathogenesis of cardiac dysfunction in hypothyroid humans has been uncertain. We evaluated a profoundly hypothyroid young man with dilated cardiomyopathy. Before and during 9 months of thyroxine therapy, serial assessment of myocardial performance documented substantial improvements in the left ventricular ejection fraction (16-37%), left ventricular end-diastolic diameter (7.8-5.9 cm), and cardiac index (1.4-2.7 liters.min-1.m-2). Steady-state levels of mRNAs encoding selected cardiac proteins were measured in biopsy samples obtained before and after thyroxine replacement. In comparison with myocardium from nonfailing control hearts, this patient's pretreatment alpha-myosin heavy-chain mRNA level was substantially lower, the atrial natriuretic factor mRNA level was markedly elevated, and the phospholamban mRNA level was decreased. All of these derangements were reversed 9 months after restoration of euthyroidism. These observations in an unusual patient with profound myxedema and cardiac dilatation permit correlation between the reversible changes in myocardial function and steady-state mRNA levels in a cardiomyopathy. They suggest that alterations in gene expression in the dilated myopathic heart may be correctable when a treatable cause is identified.

Actins↗
PubMed1992

Can we alter survival in patients with congestive heart failure?

OBJECTIVE: To assess the efficacy of pharmacologic therapy in improving survival in patients with congestive heart failure (CHF) in the context of recent investigational studies having mortality as an end point. DATA SOURCES: Data were obtained from English-language articles that reported both randomized and retrospective studies assessing the efficacy of pharmacologic therapy in the treatment of patients with CHF. The review included articles indexed under the terms congestive heart failure and drug therapy in the National Library of Medicine's MEDLINE database. STUDY SELECTION: Studies selected for detailed review were those having mortality as a primary or secondary end point. DATA EXTRACTION: Guidelines for assessing data quality and validity included study size, double-blind and randomized design, the number of end points, the sensitivity and specificity of objective measurements, and the validity of the statistical analysis. DATA SYNTHESIS: Review of the existing literature demonstrates that pharmacologic agents that improve resting hemodynamics or exercise duration in patients with CHF may not necessarily prolong survival. However, recent studies demonstrate that angiotensin-converting enzyme inhibitors prolong survival in patients with symptomatic CHF, while at the same time improving exercise capacity and left ventricular performance. Although less well tolerated, the combination of hydralazine hydrochloride and isosorbide dinitrate therapy also improves survival, but to a lesser degree. New agents show promise, but definitive assessment requires the results of large, randomized and double-blind studies having mortality as an end point. CONCLUSIONS: Mortality is an important end point in assessing the efficacy of drugs for the treatment of CHF.

Anti-Arrhythmia Agents↗
PubMed1992

Changes in the receptor-G protein-adenylyl cyclase system in heart failure from various types of heart muscle disease.

The abnormalities of the receptor-G protein-adenylyl cyclase (RCG) system in failing human myocardium as the result of 1) idiopathic dilated cardiomyopathy (IDC), 2) ischemic dilated cardiomyopathy (ISCDC), and 3) primary pulmonary hypertension (PPH) were investigated. Depending on the etiology of heart failure, abnormalities of the RCG system result from a reduced number of beta 1 receptors, uncoupling of beta 1 or beta 2 receptors, alteration of G protein function, or decreased catalytic subunit activity of adenylyl cyclase. Compared to IDC, beta 1 receptor down-regulation is less pronounced in ISCDC, and slightly more pronounced in PPH. Preliminary data suggest that beta 1 receptor down-regulation results from alteration in steady-state receptor mRNA levels. Increased functional activity of Gi protein, which seems to result from posttranslational modification, is observed in IDC and ISCDC. Altered Gi protein function may be the basis for beta-receptor uncoupling in IDC and ISCDC, whereas in PPH, this phenomenon may result from altered adenylyl cyclase function. Catalytic subunit activity of adenylyl cyclase is decreased in order of increasing pulmonary hypertension in right-ventricular preparations from PPH greater than IDC greater than ISCDC. However, catalytic subunit activity is similar in LV preparations from all three groups. The decrease in adenylyl cyclase catalytic subunit activity may be the result of the marked cellular injury produced by pressure overload. In summary, numerous desensitization phenomena occur in the failing human heart that are etiology- or model-dependent. To a certain extent, these changes are teleologically beneficial, as they are able to partially protect the failing heart from potentially toxic adrenergic stimuli.

Adenylyl Cyclases↗
PubMed1991

Detection of interleukin and interleukin-receptor mRNA in human heart by polymerase chain reaction.

Diminished cardiac contractility associated with inflammatory infiltration may be mediated by the release of interleukins. To test this hypothesis, we assessed the presence of interleukin and interleukin-receptor mRNAs in non-failing human heart and in endomyocardial biopsies from patients with dilated cardiomyopathy or inflammatory myocarditis. Only those interleukins expressed by non-circulating cells (interleukin-1 beta, -4, and -8) were detected in samples of human heart while interleukins specific for activated leukocytes (interleukins-1 alpha and -2) were not detected in any samples. While interleukin-1-receptor mRNA was present in samples from non-failing hearts and those with idiopathic myopathy, it was absent from patients with inflammatory myocarditis, suggesting receptor mRNA down-regulation.

Base Sequence↗
PubMed1991

Usefulness of OPC-8212, a quinolinone derivative, for chronic congestive heart failure in patients with ischemic heart disease or idiopathic dilated cardiomyopathy.

To evaluate the safety and efficacy of the inotropic agent OPC-8212 in patients with chronic congestive heart failure, 76 patients with impaired cardiac function and diminished exercise tolerance were studied. They were randomized to 12 weeks of double-blind therapy with either 60 mg/day of OPC-8212 or placebo. The study drug was added to their baseline medical regimen. The primary study outcome was the combined outcome of the time to either mortality (of all cause) or substantial worsening of heart failure (major morbidity), whichever occurred first. Treatment with OPC-8212 significantly (p less than 0.01) decreased the combination of major morbidity/mortality over 12 weeks of therapy. Quality of life, assessed by the Sickness Impact Profile questionnaire, was significantly improved in patients receiving OPC-8212 (p less than 0.01). Furthermore, ventricular premature contractions as assessed by 24-hour Holter monitoring were not increased with OPC-8212 treatment. Although patients treated with OPC-8212 were able to reach a significantly higher peak oxygen uptake and exercise longer during symptom-limited exercise, when data were analyzed as percent change from baseline, the absolute increases were small. These results suggest that OPC-8212 is beneficial in treating patients with congestive heart failure and that further evaluation of this new inotropic agent is warranted.

Adolescent↗
PubMed1991

Immunodetectable levels of the inhibitory guanine nucleotide-binding regulatory proteins in failing human heart: discordance with measurements of adenylate cyclase activity and levels of pertussis toxin substrate.

Human hearts with idiopathic dilated cardiomyopathy have diminished adenylate cyclase activity and increased amounts of the alpha-subunit of the inhibitory guanine nucleotide-binding regulatory protein (alpha Gi) as measured by pertussis toxin catalyzed ADP-ribosylation. We utilized specific antisera against synthetic peptides corresponding to amino sequences deduced from cDNA's encoding the three alpha Gi subspecies to compare the immunologic and bioactivity levels of Gi in failing and non-failing human hearts. The various antisera detected three peptides with Mr 42,000, 38,000, and 37,000. Only the Mr 42,000 peptide co-migrated with the pertussis toxin substrate. Although functional activity of alpha Gi was increased in the particulate fractions of the failing heart as measured by inhibition of guanine nucleotide-stimulated adenylate cyclase activity and the quantity of pertussis toxin substrate was also increased, there were not associated changes in the levels of immunodetectable Gi. Therefore, the increased functional activity of Gi in the failing human heart as assessed by adenylate cyclase measurements cannot be explained by a relative increase in the among of Gi protein.

Adenylate Cyclase Toxin↗