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Prognostic significance of atrial fibrillation in patients at a tertiary medical center referred for heart transplantation because of severe heart failure.

Atrial fibrillation (AF) occurs frequently in advanced heart failure. The prognostic significance of AF remains controversial. To determine the relation of AF to survival in patients with advanced heart failure, 234 consecutive patients referred for heart transplantation evaluation from January 1993 to June 1996 were studied to determine the effect of AF on event-free survival (freedom from death, heart transplantation, or placement of a left ventricular assist device). Clinical characteristics of the study population included: age, 51 +/- 17 years; maximum exercise oxygen consumption, 14.2 +/- 5.3 ml/kg/min; left ventricular ejection fraction, 24 +/- 11%; pulmonary capillary wedge pressure, 23 +/- 9 mm Hg; and ischemic etiology, 52%. Medical therapy included: diuretics (86%), angiotensin-converting enzyme inhibitors (80%), digoxin (80%), and anticoagulation therapy (72%). Mean duration of follow-up was 1.1 +/- 1.0 years. Sixty-two patients (27.4%) had AF. One-year event-free survival of the study population was 48%. No difference in event-free survival between patients with and without AF was observed. Univariate predictors of decreased event-free survival included: (1) advanced New York Heart Association class; (2) higher pulmonary capillary wedge pressure; (3) lower cardiac index; (4) lower maximum exercise oxygen consumption; (5) use of inotropic therapy; and (6) greater pulmonary artery systolic pressure. By multivariate analysis, independent predictors of decreased event-free survival included advanced New York Heart Association class (p <0.002) and higher pulmonary capillary wedge pressure (p = 0.02). Thus, AF in patients with advanced heart failure is not associated with decreased event-free survival.

Adult↗

Roles of renin-angiotensin and endothelin systems in development of diastolic heart failure in hypertensive hearts.

OBJECTIVE: Although interest in diastolic heart failure is growing because of its clinical frequency, little is known about this type of heart failure. Our laboratory recently developed a diastolic heart failure model using Dahl salt-sensitive rat. In this model, gene expression of angiotensin-converting enzyme and endothelin (ET) system in the left ventricle was enhanced at heart failure stage without downregulation of angiotensin type 1a receptor mRNA level. However, the roles of these humoral systems in the transition to diastolic failure remain unclear. METHODS: Subdepressor doses of angiotensin II type 1 (AT1) receptor and ET type A (ETA) receptor antagonists were administered in this model just after onset of hypertension, and their effects were investigated. RESULTS: Neither AT1 nor ETA receptor blockade inhibited the early (13 weeks) compensatory left ventricular (LV) hypertrophy. This form of compensatory hypertrophy is associated with subnormal LV end-systolic stress, which was normalized by AT1 receptor blockade but not by ETA receptor blockade. Progression of LV hypertrophy and fibrosis and transition to heart failure (19 weeks) in the untreated rats were prevented by both antagonists, resulting in normalization of LV end-diastolic pressure and lung weight. AT1 receptor blockade, but not ETA receptor blockade, normalized time constant of LV relaxation. Enhanced gene expression for ET system in the left ventricle observed in the untreated rats was suppressed with AT1 receptor antagonist administration. ETA receptor blockade slightly but significantly elevated the AT1a receptor mRNA level as compared with the untreated rats. CONCLUSIONS: RAS and ET system contribute to the transition to diastolic heart failure through the development of excessive hypertrophy and ventricular fibrosis in hypertensive heart diseases, however, neither RAS nor ET system is mandatory for normal compensation for pressure overload. RAS apparently causes such diastolic effects at least partly through the ET system.

Angiotensin Receptor Antagonists↗

Cardiac effects of the extract and active components of radix stephaniae tetrandrae. II. Myocardial infarct, arrhythmias, coronary arterial flow and heart rate in the isolated perfused rat heart.

The primary purpose of the present study was to compare the cardioprotective effects of the extract from radix stephaniae tetrandrae (RST) and its individual compounds, tetrandrine (Tet) and fanchinoline (Fan). Secondly, we also compared the cardiac effects of the individual compounds and the RST extract with those of verapamil, a classical Ca2+ channel blocker. The Langendorff isolated perfused rat heart preparation was used. Regional ischaemia and reperfusion was employed to induce myocardial infarct and arrhythmia. Infarct, arrhythmia, heart rate and coronary artery flow were determined in hearts treated with vehicle, RST extract, Tet, Fan, or verapamil. It was found that RST extract, of which only 9% was Tet, and Tet alone produced equally potent ameliorating effects on arrhythmia and infarct induced by ischaemia and reperfusion without further inhibiting ischaemia-reduced heart rate and coronary artery flow. Fan had no effects on arrhythmia and infarct induced by ischaemia and reperfusion; but it induced S-T segment elevation and further reduced heart rate and coronary artery flow during ischaemia. Verapamil also ameliorated the effects of ischaemia and reperfusion on arrhythmia and infarct. It should be noted that 1 microM verapamil, that produced comparable effects on infarct and arrhythmia to the RST extract and Tet, further inhibited heart rate during ischaemia. The results indicate that the RST extract produces equally potent cardioprotective and anti-arrhythmic effects as Tet alone. Both RST extract and Tet may be better choices for the treatment of arrhythmia and infarct induced by myocardial ischaemia and reperfusion than the classical Ca2+ channel blocker, verapamil as they do not further reduce heart rate during ischaemia.

Alkaloids↗

Cardiac autonomic denervation in congestive heart failure: comparison of Chagas' heart disease with other dilated cardiomyopathy.

Congestive heart failure (CHF) is associated with activation of the cardiac sympathetic nerves. However, impairment of the sympathetic nerve terminals in patients with CHF has been indicated by studies showing reduction of cardiac norepinephrine uptake and stores. This investigation studies the histochemical evaluation of the sympathetic nerve terminals in CHF. The cardiac parasympathetic innervation was also studied to address the question of specificity of the presumed sympathetic denervation. Nineteen patients with CHF underwent cardiac transplantation or partial ventriculectomy, which provided the heart tissue. In 11 of them, the dilated cardiomyopathy was associated with Chagas' disease. Inflammatory process and fibrosis were studied histologically. The sympathetic and parasympathetic nerve fibers were visualized through histochemical techniques for, respectively, catecholamines and acetylcholinesterase activity. By using a computer-assisted morphometric program, the inflammation, fibrosis, and parasympathetic innervation were quantified. Moderate to severe fibrosing myocarditis characterized the hearts of the chagasic patients. In cardiomyopathies not associated with Chagas' disease, the inflammation was discrete, if present, but the amount of fibrosis was similar to that found in Chagas' cardiomyopathy. Reduction of both kinds of nerve terminals occurred in the heart of all patients. The parasympathetic denervation was proven to be more severe in chagasic cardiomyopathy. Our data on the heart innervation indicate a progressive autonomic denervation in heart failure. In Chagas' heart disease, the denervation seems to be more severe or rapid, probably because of the sustained inflammatory process.

Acetylcholinesterase↗

Effect of heart transplantation on impaired peripheral microvascular perfusion and reactivity in congestive heart failure.

Whether reduced peripheral blood flow in congestive heart failure is reversed after heart transplantation, has not been closely examined. We therefore studied skin microvascular resting perfusion and reactivity in patients pre- and postoperatively. Resting digital skin perfusion, together with the responses to cold pressor test, postocclusive reactive hyperemia and direct skin heating were examined with laser Doppler perfusion measurements. We examined 28 patients with congestive heart failure and 14 of these patients after heart transplantation and compared them to 13 healthy controls. Measurements were performed within 3 months preoperatively and 12 days, 1, 2, 3 and 6 months postoperatively. Patients with congestive heart failure had significantly lower resting perfusion levels than controls and demonstrated attenuated responses to both stimuli of vasodilation (all P<0.01). While peak hyperemic responses improved significantly after transplantation, postocclusive area under the hyperemic curve decreased further, and none of these variables were normalized after 6 months. In contrast, minimal perfusion during cold pressor test increased from a significantly lower level in the patients with congestive heart failure (P<0.05), to a level similar to that of the controls within 12 days postoperatively. Thus, skin microvascular perfusion and reactivity improve, but are not normalized within 6 months of transplantation. Both pre- and postoperative factors may be involved in maintaining a dysfunction of the peripheral microcirculation, which may contribute to exercise intolerance and hypertension in heart transplant recipients.

Adult↗

Confirmation of a heart failure epidemic: findings from the Resource Utilization Among Congestive Heart Failure (REACH) study.

OBJECTIVES: The purpose of this study was to create an automated surveillance tool for reporting the incidence, prevalence and processes of care for patients with heart failure. BACKGROUND: Previous epidemiologic studies suggest that the increasing prevalence of heart failure is a consequence of improved survival coupled with minimal changes in disease prevention. Developing new, efficient methods of assessing the incidence and prevalence of heart failure could allow continued surveillance of these rates during an era of rapidly changing treatments and health care delivery patterns. METHODS: Using administrative data sets, we created a definition of heart failure using diagnosis codes. After adjustment for patients leaving our health system or death, we derived the incidence, prevalence and mortality of the population with heart failure from 1989 to 1999. RESULTS: A total of 29,686 patients of all ages, 52.6% women and 47.4% men, met the definition of heart failure. Mean ages were 71.1 +/- 14.5 for women and 67.7 +/- 14.4 for men, p < 0.0001. Race proportions were 50.5% white, 44.6% African American and 4.9% other race. Incidence rates were higher in men and African Americans across all age groups. There was an annual increase in prevalence of 1/1,000 for women and 0.9/1,000 for men, p = 0.001 for both trends. CONCLUSIONS: Through the feasible and valid use of automated data, we have confirmed a chronic disease epidemic of heart failure manifested primarily by an increase in prevalence over the past decade. Our surveillance system mirrors the results of epidemiologic studies and may be a valid method for monitoring the impact of prevention and treatment programs.

Black or African American↗

Heart rate is a marker of amiodarone mortality reduction in severe heart failure. The GESICA-GEMA Investigators. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina-Grupo de Estudios Multicéntricos en Argentina.

OBJECTIVES: The impact of amiodarone on mortality in patients with severe congestive heart failure (CHF) (New York Heart Association functional classes II [advanced], III and IV; left ventricular ejection fraction < 35%) In the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) trial was analyzed in relation to initial mean baseline heart rate (BHR) and its change after 6 months of follow-up. BACKGROUND: Trials of amiodarone therapy in CHF have produced discordant results, suggesting that the effect is not uniform in all patient subgroups with regard to survival. METHODS: The present analysis was carried out in 516 patients randomized to receive amiodarone, 300 mg/day (n = 260), or nonantiarrhythmic therapy (n = 256, control group) and followed up for 2 years. Survival was evaluated for patients with a BHR > or = 90 beats/min (control: n = 132; amiodarone: n = 122) and < 90 beats/min (control: n = 124; amiodarone: n = 138). Survival was also analyzed according to heart rate reduction at 6 months for 367 patients. RESULTS: For patients with a BHR > or = 90 beats/min, amiodarone therapy reduced mortality to 38.4% compared with 62.4% in control patients (relative risk [RR] 0.55, 95% confidence interval [CI] 0.35 to 0.95, p < 0.002). Both sudden death (RR 0.46, 95% CI 0.24 to 0.90, p < 0.02) and progressive heart failure death (RR 0.60, 95% CI 0.30 to 1.03, p < 0.06) were reduced, and functional capacity was improved. In patients with a BHR < 90 beats/min, amiodarone did not alter survival. Among 367 patients who completed 6 months of follow-up, amiodarone reduced 2-year mortality only in those with a BHR > or = 90 beats/min, which was reduced at 6 months. CONCLUSIONS: Elevated rest heart rates in severe CHF identify a subgroup of patients who benefit from treatment with amiodarone. Amiodarone-induced heart rate slowing may be an important benefit for patients.

Amiodarone↗

Incomplete sympathic reinnervation of the orthotopically transplanted human heart: observation up to 13 years after heart transplantation.

OBJECTIVE: Heart transplantation (HTx) is associated with autonomic denervation of the donor heart. Sympathetic reinnervation (RI) as defined by the presence of functional nerve terminals occurs only if sympathetic ganglia outside the heart are connected with nerve terminals in the transplanted heart. The purpose of this study was to define the incidence and functional consequences of RI over time after HTx. The activity and distribution of norepinephrine (NE) uptake sites were assessed by positron emission tomography (PET) imaging. Symptom limited exercise testing was performed by bicycle-ergometer. METHODS: Forty-seven patients (m:f=42:5, 47.6+/-8. 2 years, age range 27-65 years) were investigated between 2 months and 13.6 years after HTx using PET and the NE analogue C-11-hydroxyephedrine (HED). Tracer uptake was quantified using dynamic imaging protocols yielding regional HED retention fraction. A regional value above 7%/min (+/-2.5 SD above the mean value of denervated hearts) was considered evidence for RI. The functional significance of RI was investigated in 34 patients (m:f=30:4, 49. 3+/-8.4 age range 27-62 years) by symptom limited exercise testing. Cardiac catheterization was performed at the time of PET imaging. RESULTS: RI could not be assessed in the first year after HTx, in 11% in the second year and in 80% of the patients from the third year on. Retention values plateaued then. In all time intervals, beyond the third year, not reinnervated patients were found. RI remained incomplete and was always restricted to the anterior wall of the left ventricle. Extent of retention of the left ventricle revealed a large individual range up to 66%, averaging of 20%. Recipient age at the time of HTx, reinnervated patients were 5.5 years younger than not reinnervated ones, proved as the only significant influencing factor for RI (P<0.05). Dividing patients into scintigraphically reinnervated (n=20) and not reinnervated (n=14), reinnervated patients displayed during exercise a higher maximal heart rate (137+/-14 vs. 123+/-20/min, P<0.05), heart rate increase (40+/-15 vs. 28+/-13/min, P<0.05), max. oxygen consumption (1674+/-424 vs. 1279+/-308 ml/min, P<0.01) and anaerobic threshold (887+/-170 vs. 717+/-183 mlO(2)/min, P<0.01) than not reinnervated ones. A correlation between transplant vasculopathy and RI could not be demonstrated. CONCLUSION: ++: RI assessed by PET and the NE analogue HED is time dependent, incomplete, displays a typical pattern and demonstrates a broad individual spread. Furthermore, RI enhances functional parameters of exercise testing.

Carbon Radioisotopes↗

Reversible pulmonary hypertension in heart transplant candidates--pretransplant evaluation and outcome after orthotopic heart transplantation.

BACKGROUND: Heart transplantation is the most effective treatment for well-selected patients with endstage heart failure. Unfortunately, transplant candidates with pulmonary hypertension (PHT) are often not considered for heart transplantation. This study was performed to assess the value of prostaglandin E(1) (PG-E(1)) for reduction of PHT and to predict the postoperative outcome, compared to patients without PHT. PATIENTS AND METHODS: We studied a group of 151 consecutive heart transplant candidates using right heart catheterization. In patients with PHT (pulmonary vascular resistance, PVR> or =2.5 Wood-Units (WU) and/or transpulmonary gradient (TPG)> or =12 mmHg) a short-term treatment protocol with PG-E(1) was performed, to achieve PVR<2.5 WU and TPG<12 mmHg. RESULTS: 61 patients (40%) had PHT according to our criteria. Reduction of PHT was successful in 71% of patients (n=43), of these, 18 patients underwent cardiac transplantation and the 1-year mortality rate was 22% (n=4). The 1-year mortality rate in transplanted patients without PHT was 14% (n=3). There was no statistical difference in survival between the PHT and the non-PHT group. Outcome in patients without heart transplantation was similar in both groups, except for patients with non-reducible PHT (1-year mortality 50%). CONCLUSIONS: Our study demonstrates the efficacy and safety of PG-E(1) in lowering PHT in heart transplant candidates, as well as the need for aggressive evaluation and treatment in these patients. Patients with reversible PHT have comparable post-transplant outcomes and no tendency to higher acute right ventricular failure.

Alprostadil↗

Is heart rate variability an objective parameter with which to manage treatment of infants with heart failure due to left-to-right shunting?

Treatment in heart failure could be guided by additional non-clinical measures, such as neurohumoral levels. Variability in heart rate is known to reflect neurohumoral stimulation. With this in mind, we sought to assess retrospectively the variability in heart rate to guide the treatment of infants in heart failure. We analysed retrospectively the data from 20 infants with a significant left-to-right shunt. All were unsuitable for cardiac surgery or interventional therapy at the time the treatment had commenced. None of the infants improved while receiving diuretics, spironolactone, and digoxin alone, but improved after the addition of propanolol or metoprolol. None of the infants had problems during or after the subsequent operation. Parasympathetic activity reflected by parameters of variability in heart rate, such as the square root of adjacent RR-intervals, and the amount of adjacent RR-intervals greater than 50 milliseconds, improved in nearly all infants during beta blockade. On the other hand, parameters of variability in heart rate reflecting sympathetic activity did not change. Parasympathetic activity reflected the clinical state of nearly all the infants. These parameters, therefore, seem to be a good non-clinical parameter, showing the optimal treatment for heart failure in an ambulatory setting.

Heart Failure↗

An investigation of the oral status and reported oral care of children with heart and heart-lung transplants.

AIM: To investigate the oral health status and oral microflora of children who have received heart and heart-lung transplants. Parental knowledge and current practice of oral health procedures by the child were also investigated. SAMPLE AND METHOD: Thirty-five children attending the Cardio-Thoracic Transplant Unit, Great Ormond Street Hospital for Children were included. Measurements were compared with children matched by age and gender attending the trauma clinic at the Department of Paediatric Dentistry, Eastman Dental Hospital. Teeth were examined for the presence or absence of caries or enamel defects. Plaque deposition, gingivitis, gingival bleeding and gingival enlargement were measured and a swab was taken to look at the oral microbial flora. A questionnaire was used to assess parental knowledge of dental health procedures and the current practice of these. RESULTS: There were no significant differences between transplant and control children in caries experience, plaque or gingivitis. Children with heart or heart-lung transplants had significantly greater numbers of enamel defects and more gingival enlargement than control children, children in the heart transplant group had significantly more gingival bleeding. There was little difference in the dental knowledge and reported behaviour of the transplant group compared to the control group. CONCLUSION: The dental needs of heart and heart-lung transplant patients treated at the Great Ormond Street Hospital for Children were similar to those of the control group in this study, however further improvement could be made in educating parents and children on the importance of caries prevention and good oral hygiene.

Adolescent↗

Heart period and heart period variability during sleep on the MIR space station.

The long-term acclimation of cardiac rhythms to microgravity was studied in four astronauts aboard the Russian space station MIR during wakefulness and sleep. Sleep polygraphies were obtained between the third and the 30th day in space and, in addition, prior to mission on the ground. From each of the sleep polygraphies, beat-to-beat intervals of cardiac rhythms were determined. The response of heart period and heart period variability to the stimulus microgravity was tested during sleep across sleep stages and during waking. A lengthening of heart period by about 100 ms was found in space compared to measurements on the ground. The slowing of heart rate was more pronounced for non-REM sleep than for REM sleep. A systematic change in heart period in relation to the duration of the stay in space could not be detected. An analysis of heart period variability in the high frequency (respiratory sinus arrhythmia) band supports the hypothesis that the decrease of heart rate under microgravity is produced by an increase in parasympathetic activity. Testing the response of cardiac rhythms to microgravity across distinct behavioural states seems to be a powerful tool to investigate the cardiovascular system.

Adult↗

Heart rate and heart rate variability changes in the intracarotid sodium amobarbital test.

PURPOSE: Changes in heart rate and heart rate variability have been found in prior studies performed during the intracarotid sodium amobarbital (ISA) test. However, these results are not entirely consistent with current models of differential cerebral involvement in the modulation of the heart. This study was designed to re-investigate this topic with a larger N than has heretofore been used. METHODS: The electrocardiogram was recorded during left and right ISAs in 73 subjects. Raw heart rate and heart rate variability were calculated. RESULTS: Raw heart rate increased during inactivation of either hemisphere, but more so for the right hemisphere. Heart rate variability changes consistent with decreasing parasympathetic tone also were found to occur during either ISA, but to a significant degree, only during right ISA. CONCLUSIONS: The right hemisphere appears to have a greater role in cerebral regulation of cardiac function, perhaps by virtue of the modification of parasympathetic effects.

Adolescent↗

Defining the optimum upper heart rate limit during exercise: a study in pacemaker patients with heart failure.

AIMS: There is no non-invasive method to determine the individual optimum of maximum exercise heart rate. Knowledge of this value is of particular interest in patients with structural heart disease who are prone to tachycardia intolerance. The purpose of this study was to define the optimal maximum heart rate using cardiopulmonary exercise testing and exercise Doppler echocardiography and to compare the results of both approaches. METHODS AND RESULTS: In 49 pacemaker patients with chronotropic incompetence, the optimum upper heart rate limit was determined using cardiopulmonary exercise testing and exercise Doppler echocardiography. The optimum upper rate limit was given by the highest pacing rate which still produced an increase in oxygen consumption, or by that pacing rate which was linked to the lowest value for the Doppler-derived myocardial performance index. In patients with normal left ventricular ejection fraction (>or=55%) the optimum upper rate limit was 86% of age-predicted maximum heart rate, in patients with left ventriuclar dysfunction (ejection fraction <or=45%) it was 75% of the age-predicted maximum rate (P=0.004). The optimum upper rate limit, as defined by cardiopulmonary exercise testing and exercise Doppler echocardiography, were closely correlated (P<0.0001) with a mean deviation of 6+/-6 beats x min(-1). CONCLUSION: Cardiopulmonary exercise testing and exercise Doppler echocardiography are valuable tools which help to determine the optimum upper rate limit in order to avoid excess heart rates in heart failure patients. The application of these methods is not limited to pacemaker patients but may be helpful in therapeutic interventions with chronotropic drugs.

Adult↗

Heart rate during a defined exercise test in horses with heart and lung diseases.

During a gradually increasing exercise test heart rates were determined in healthy animals and in 2 groups of sick horse. These included 31 animals with a chronic pulmonary disorder and 5 with chronic heart disease. The alteration in heart rate was correlated with the clinical signs exhibited. In the horses with lung disease there was a close correlation between the stage of the diseases and the heart rate during the exercise test. In 3 animals with heart valve disease there was no apparent difference in heart rate compared with healthy horses. On the other hand the exercising heart rate of horses with atrial fibrillation showed a significant increase. The recovery rate of pulse and respiration after a 20 min trot did not show any correlation with the stage of disease or the pulse and respiration after a 20 min trot did not show any correlation with the stage of disease or the results of gradually stepping up the exercise in horses with lung disease.

Animals↗

Paradox of circulating advanced glycation end product concentrations in patients with congestive heart failure and after heart transplantation.

OBJECTIVES: To analyse circulating concentrations of advanced glycation end products (AGEs) in patients with severe congestive heart failure (CHF) and after heart transplantation; to identify the potential contribution of kidney function to plasma AGE concentrations; and to determine whether AGE concentrations and parameters of oxidative stress are interrelated. METHODS AND RESULTS: Circulating N(epsilon)-(carboxymethyl)lysine (CML) and AGE associated fluorescence (AGE-Fl), lipid peroxidation, and glomerular filtration rate (GFR) were measured in a cross sectional study of 22 patients with advanced CHF, 30 heart transplant recipients, and 20 healthy controls. Compared with the controls, the CHF patients had decreased CML (mean (SEM) 467.8 (20.0) ng/ml v 369.3 (22.3) ng/ml, p < 0.01), AGE-Fl (mean (SEM) 302.2 (13.3) arbitrary units v 204.9 (15.7) arbitrary units, p < 0.01), and GFR (p < 0.01). CML was positively related to decreased total protein and serum albumin and negatively to body mass index (p < 0.01). In contrast, in the heart transplant group, impaired GFR was associated with a notable rise of both CML (mean (SEM) 876.1 (53.1) ng/ml, p < 0.01) and AGE-Fl (mean (SEM) 385.6 (26.1) arbitrary units, p < 0.01). A positive relation between CML and serum albumin (r = 0.394, p < 0.05) and lipofuscin (r = 0.651, p < 0.01) was found. CONCLUSIONS: The contrasting concentration of CML and AGE-Fl between patients with CHF and after heart transplantation in the presence of decreased GFR and oxidative stress are explained by lowered plasma proteins in CHF and higher concentrations in heart transplant recipients. In heart transplant recipients, in addition to myocardial inflammatory processes, immunosuppression may be important for enhanced formation of AGEs.

Adolescent↗

Heart rate-independent energetics and systolic pressure-volume area in dog heart.

Left ventricular (LV) systolic pressure-volume area (PVA), a new measure of total mechanical energy for the contraction, linearly correlates with its oxygen consumption per beat (VO2) regardless of contraction mode in a canine heart with stable chronotropism and inotropism. PVA is the area in the pressure-volume (PV) diagram circumscribed by the end-systolic and end-diastolic PV relation curves and the systolic segment of the PV loop and has dimensions of energy. We investigated whether primary changes in heart rate would affect the VO2-PVA relation. In the excised cross-circulated canine heart with left ventricular load controlled with a servo pump, we changed heart rate by pacing to compare the VO2-PVA relations at low [124 +/- 17 (SD) min-1] and high (193 +/- 23) heart rates. In 15 left ventricles, VO2 (ml O2 X beat-1 X 100 g LV-1) was (1.75 +/- 0.57) X 10(-5) PVA (mmHg X ml X beat-1 X 100 g LV-1) + 0.031 +/- 0.011 (ml O2 X beat-1 X 100 g LV-1). The VO2-PVA relation was virtually independent of heart rate in individual hearts. We conclude that the load-independent VO2-PVA relationship is not affected by chronotropism in a given canine left ventricle.

Animals↗

QTL associated with blood pressure, heart rate, and heart weight in CBA/CaJ and BALB/cJ mice.

To better understand the genetic basis of essential hypertension, we conducted a quantitative trait locus (QTL) analysis of a population of 207 (BALB/cJ x CBA/CaJ) F(2) male mice to identify genomic regions that regulate blood pressure, heart rate, and heart weight. We identified two loci, Bpq6 (blood pressure quantitative locus 6) on chromosome 15 (Chr 15; peak, 16 cM; 95% confidence interval, 0-25 cM) and Bpq7 on Chr 7 (peak, 42 cM; 95% confidence interval, 35-50 cM) that were significantly associated with blood pressure. We also identified two loci, Hrq1 (heart rate quantitative locus 1) and Hrq2, on D2Mit304 (peak, 72 cM; 95% confidence interval 60-80 cM) and D15Mit184 (peak, 25 cM; 95% confidence interval 20-35 cM), respectively, that were significantly associated with heart rate. A significant gene-gene interaction for heart rate was found between Hrq1 and D1Mit10 (peak, 57 cM; 95% confidence interval, 45-75 cM); the latter QTL was named Hrq3. We identified a significant locus for heart weight, Hwq1 (heart weight quantitative locus 1), at D14Mit67 (peak, 38 cM; 95% confidence interval, 20-43 cM). Identification of the genes for these QTL should lead to a better understanding of the causes of essential hypertension.

Animals↗