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Rapid brain natriuretic peptide test and Doppler echocardiography for early diagnosis of mild heart failure.

BACKGROUND: The early identification of patients at risk for the development of clinical heart failure (HF) is a new challenge in an effort to improve outcomes. METHODS: We prospectively evaluated whether the combination of brain natriuretic peptide (BNP) measurements (Triage BNP test, Biosite Diagnostics) and echocardiography would effectively stratify patients with new symptoms in a cost-effective HF program aimed at early diagnosis of mild HF. A total of 252 patients were referred by 100 general practitioners. RESULTS: Among the study population, the median BNP value was 78 ng/L (range, 5-1491 ng/L). BNP concentrations were lower among patients without heart disease [median 15 ng/L (range, 5-167 ng/L); n = 96] than among patients with confirmed HF [median, 165 ng/L (22-1491 ng/L); n = 157; Mann-Whitney U-test, 12.3; P <0.001]. Patients were grouped into diastolic dysfunction [BNP, 195 (223) ng/L], systolic dysfunction [BNP, 290 (394) ng/L], and both systolic and diastolic dysfunction [BNP, 776 (506) ng/L]. In this model, a cutoff value of 50 ng/L BNP increases the diagnostic accuracy in predicting mild HF, avoiding 41 echocardiograms per 100 patients studied, with a net saving of 14% of total costs. CONCLUSIONS: Blood BNP concentrations, in a cost effective targeted screening, can play an important role in diagnosing mild HF and stratifying patients into risk groups of cardiac dysfunction.

Adult↗

[Arterial hypertension and systolic left ventricular dysfunction: therapeutic approach].

Arterial hypertension is a cardinal precursor of congestive heart failure, and diastolic dysfunction is the most frequent mechanism for it. Systolic left ventricular dysfunction, although less frequent, has a worse prognosis. Most cases of systolic dysfunction in patients with hypertension is due to acute myocardial infarction, although other mechanisms can be involved. In some studies, non-ischemic hypertensive systolic dysfunction is the etiology of chronic heart failure in up to 10% of patients with dilated cardiomyopathy. Diastolic dysfunction and left ventricular hypertrophy are also associated with a higher risk of heart failure and systolic dysfunction. Given the poor prognosis of patients with congestive heart failure and dilated cardiomyopathy, it is fundamental to try to prevent the development of left ventricular dysfunction by means of a correct control of blood pressure, regression of left ventricular hypertrophy and prevention of coronary artery disease. When systolic dysfunction is established, angiotensin converting enzyme inhibitors are the treatment of choice; diuretics and digoxin can be added in patients with overt congestive heart failure. Recent studies suggest that other drugs, such as carvedilol and losartan, can be beneficial, but current evidence is still scarce.

Amlodipine↗

Independent and incremental prognostic value of Doppler-derived mitral deceleration time of early filling in both symptomatic and asymptomatic patients with left ventricular dysfunction.

OBJECTIVES: This study sought to investigate the relative and incremental prognostic value of demographic, historical, clinical, echocardiographic and mitral Doppler variables in patients with left ventricular systolic dysfunction. BACKGROUND: The prognostic value of diastolic abnormalities as assessed by mitral Doppler echocardiography has yet to be defined. METHOD: A total of 508 patients with left ventricular ejection fraction < or = 35% were followed up for a mean (+/- SD) period of 29 +/- 11 months. RESULTS: During the follow-up period, 148 patients (29.1%) were admitted to the hospital for congestive heart failure, and 100 patients (19.7%) died. By Cox model analysis, Doppler-derived mitral deceleration time of early filling < or = 125 ms (relative risk [RR] 1.93, 95% confidence interval [CI] 1.4 to 3.7), New York Heart Association functional class III or IV (RR 1.49, 95% CI 1.4 to 2.3), ejection fraction < or = 25% (RR 1.85, 95% CI 1.6 to 2.9), third heart sound (RR 2.06, 95% CI 1.8 to 3.2), age > 60 years (RR 1.95, 95% CI 1.8 to 3.1) and left atrial area > 18 cm2 (RR 1.73, 95% CI 1.6 to 2.7) were all found to be independent and additional predictors of all-cause mortality, and deceleration time was the single best predictor (chi-square 37.80). When all these significant variables were analyzed in hierarchic order, after age, functional class, third sound, ejection fraction and left atrial area, deceleration time still added significant prognostic information (global chi-square from 9.2 to 104.7). Also, deceleration time was the strongest independent predictor of hospital admission for congestive heart failure (RR 4.88, 95% CI 3.7 to 6.9) and cumulative events (congestive heart failure or all-cause mortality, or both; RR 2.44, 95% CI 2.0 to 3.8) in both symptomatic and asymptomatic patients. CONCLUSIONS: Deceleration time of early filling is a powerful independent predictor of poor prognosis in patients with left ventricular systolic dysfunction, whether symptomatic or asymptomatic. A short (< or = 125 ms) deceleration time by mitral Doppler echocardiography adds important prognostic information compared with other clinical, functional and echocardiographic variables.

Cohort Studies↗

Congestive heart failure with preserved left ventricular systolic function after acute myocardial infarction: clinical and prognostic implications.

AIMS: To characterise the prevalence, in-hospital complications, management, and long-term outcome of patients with congestive heart failure but preserved left ventricular systolic function after acute myocardial infarction. METHODS: 3166 consecutive patients screened for entry in the Bucindolol Evaluation in Acute Myocardial Infarction Trial with definite acute myocardial infarction and echocardiographic assessment of left ventricular systolic function were included between 1998 and 1999 in this prospective observational study. Main outcome measures were occurrences of in-hospital complications and all cause mortality. RESULTS: Congestive heart failure was seen during hospitalisation in 1464 patients (46%), 717 patients had preserved left ventricular systolic function (wall motion index > or =1.3 corresponding to ejection fraction > or =0.40), and 732 patients had systolic dysfunction (wall motion index <1.3). One year mortality in patients with no heart failure, heart failure with preserved systolic function, and heart failure with systolic dysfunction were 6, 22 and 35%, P<0.0001. Unadjusted risk of death from all causes associated with heart failure and preserved systolic function was 3.3 (95% CI 2.8-4.0), and after adjustment for baseline characteristics and left ventricular systolic function in multivariate Cox proportional hazards analysis the risk was 2.1 (95% CI 1.7-2.6), P<0.0001. CONCLUSIONS: Congestive heart failure is frequently present in patients with preserved left ventricular systolic function, and is associated with increased risk of in-hospital complications and death following acute myocardial infarction.

Aged↗

Reduced systolic myocardial function in children with chronic renal insufficiency.

Increased left ventricular (LV) mass in children with chronic renal insufficiency (CRI) might be adaptive to sustain myocardial performance in the presence of increased loading conditions. It was hypothesized that in children with CRI, LV systolic function is impaired despite increased LV mass (LVM). Standard echocardiograms were obtained in 130 predialysis children who were aged 3 to 18 yr (59% boys) and had stages II through IV chronic kidney disease and in 130 healthy children of similar age, gender distribution, and body build. Systolic function was assessed by measurement of fractional shortening at the endocardial (eS) and midwall (mS) levels and computation of end-systolic stress (myocardial afterload). The patients with CRI exhibited a 6% lower eS (33.1 +/- 5.5 versus 35.3 +/- 6.1%; P < 0.05) and 10% lower mS (17.8 +/- 3.1 versus 19.7 +/- 2.7%; P < 0.001) than control subjects in the presence of significantly elevated BP, increased LVM, and more concentric LV geometry. Whereas the decreased eS was explained entirely by augmented end-systolic stress, mS remained reduced after correction for myocardial afterload. The prevalence of subclinical systolic dysfunction as defined by impaired mS was more than five-fold higher in patients with CRI compared with control subjects (24.6 versus 4.5%; P < 0.001). Systolic dysfunction was most common (48%) in patients with concentric hypertrophy and associated with lower hemoglobin levels. CRI in children is associated with impaired intrinsic LV contractility, which parallels increased LVM.

Adolescent↗

Atrial fibrillation as a cause of left ventricular dysfunction after cardiac transplantation.

We report 3 cases of late-onset atrial fibrillation several years after cardiac transplantation, each involving left ventricular systolic dysfunction in the absence of cardiac rejection or cardiac allograft vasculopathy. Although the etiology of late-onset atrial fibrillation in cardiac transplant recipients is not clear, its presence in the absence of cardiac rejection or coronary allograft vasculopathy can result in left ventricular systolic dysfunction, and therefore should be considered in the differential diagnosis of cardiac allograft failure. The onset of atrial fibrillation years after a heart transplant is not necessarily an indication of rejection. Aggressive rate control and restoration of normal sinus rhythm may improve allograft function in such cases.

Atrial Fibrillation↗

Relation between reversal of diastolic creep and recovery of systolic function after ischemic myocardial injury in conscious dogs.

Although prolonged functional abnormalities after transient myocardial ischemia have been well described, the interrelationship between postischemic systolic and diastolic alterations remains controversial. Therefore, 24 chronically instrumented conscious dogs were studied with left ventricular and pleural micromanometers, ultrasonic dimension transducers in the left anterior descending (LAD) coronary distribution, and vena caval and coronary artery occluders. The LAD was occluded for 15 minutes and reperfused for 24 hours while vena caval occlusions were performed at intervals to measure myocardial segment length at 0 mm Hg transmural diastolic left ventricular pressure (L0). Coronary occlusion produced an immediate fall in systolic function as assessed by ejection shortening and stroke work and also induced a 16 +/- 4% increase in L0, which was termed diastolic creep. Throughout reperfusion, reversal of diastolic abnormalities correlated strongly with recovery of segmental shortening and stroke work (p less than 0.001). Correlation between systolic dysfunction and diastolic creep was also observed during alteration of inotropic state by dopamine, during initial reperfusion hyperfunction, and during pharmacologic manipulation of afterload. In 5 additional dog hearts fixed in diastole by rapid glutaraldehyde infusion after coronary occlusion, myocardial creep measured by the segment length transducers paralleled sarcomere elongation measured by electron microscopy. Thus, the direct correlation between diastolic creep and systolic dysfunction throughout reperfusion and during hemodynamic alterations suggests that diastolic properties of postischemic myocardium may not be entirely passive and that systolic and diastolic dysfunction induced by ischemia may have a common basis at the cellular level.

Animals↗

Treatment of asymptomatic patients with left ventricular dysfunction.

Results of the SOLVD prevention trial and of the SAVE trial indicate that long-term treatment with ACE inhibitors in asymptomatic patients with LV systolic dysfunction prevents the progression to overt CHF and reduces hospitalizations for CHF. ACE inhibitors have been shown to reduce mortality in at least some subsets of asymptomatic patients with LV systolic dysfunction, notably those with recent myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

Diastolic dysfunction is associated with anaemia in patients with Type II diabetes.

Anaemia is common in patients with diabetes and associated with an increased risk of diabetic complications. Although the role of anaemia in heart failure is established, we hypothesize that anaemia also contributes to an increased risk of cardiac dysfunction in patients with Type II diabetes. In the present study, 228 consecutive adults with diabetes were investigated using transthoracic echocardiography. Echocardiographic parameters were correlated with the Hb (haemoglobin) level and adjusted for other risk factors for cardiac dysfunction using multivariate analysis. More than one in five patients (23%) had anaemia, which was an independent risk factor for cardiac dysfunction on echocardiography. Over one-third of all patients with evidence of abnormal cardiac function (diastolic and/or systolic dysfunction) on echocardiography had anaemia compared with <5% of patients with normal echocardiographic findings. Most patients with anaemia had cardiac dysfunction (94%), with the major abnormality being diastolic dysfunction associated with an increased left ventricular mass and impaired relaxation indices. A continuous association between diastolic function and Hb was also observed in patients without anaemia. In patients with a history of cardiovascular disease, systolic dysfunction was twice as common in patients with anaemia. Anaemia was also correlated with plasma markers of cardiac risk, including BNP (brain natriuretic peptide), CRP (C-reactive protein) and AVP (arginine vasopressin). Notably, the predictive utility of these markers was eliminated after adjusting for Hb. Consequently, the inexpensive measurement of Hb may be a useful tool to identify diabetic patients at increased risk of cardiac dysfunction.

Aged↗

Diastolic dysfunction.

Diastolic dysfunction of the heart is characterized by normal left ventricular contractility and normal ejection fraction, however ventricular relaxation is impaired. In systolic dysfunction, ventricular contractility and ejection fraction are reduced, in addition to impaired relaxation. The prevalence of diastolic dysfunction is increased in the elderly, especially those who have had inadequately treated hypertension. Both diastolic and systolic dysfunction may result in similar clinical signs and symptoms. Therefore, echocardiography is needed to make the distinction. Left atrial (LA) enlargement, assessed by left atrial volume indexed to body surface area, appears to be the best measure to assess diastolic function. LA enlargement is likely when indexed LA volume is > or = 34-40 mL/m2. B-type natriuretic protein appears to be useful for the diagnosis, assessment and prognosis of heart failure, but it does not distinguish between the two types of dysfunctions. Several drug treatments that have effects on the mechanism of diastolic dysfunction are under investigation.

Adult↗

Open access echocardiography in management of heart failure in the community.

OBJECTIVE: To assess the value of an open access echocardiography service. DESIGN: Study of new open access service for general practitioners, who were invited to refer patients taking diuretics for suspected heart failure, untreated patients with symptoms of possible heart failure, and asymptomatic patients with risk factors for left ventricular systolic dysfunction. SETTING: Regional cardiology centre. SUBJECTS: 259 consecutive patients. MAIN OUTCOME MEASURES: Presence or absence of left ventricular systolic dysfunction and consequent changes in clinical management. RESULTS: 119 treated patients, 99 untreated patients, and nine asymptomatic patients were referred over five months. 32 were considered to be inappropriately referred. Among the treated patients, 31 had impaired left ventricular systolic function and five had valvular disease; angiotensin converting enzyme inhibitors were recommended for 34 of these patients. In addition, 53 were thought not to need diuretics. Eight untreated patients had impaired systolic function and six valvular disease. CONCLUSIONS: The service was well used by general practitioners and led to advice to change management in more than two thirds of patients.

Adolescent↗

Rapid titration of carvedilol in patients with congestive heart failure: a randomized trial of automated telemedicine versus frequent outpatient clinic visits.

BACKGROUND: Because of potential side effects and logistical difficulty of titrating medications, outpatients with congestive heart failure rarely receive appropriate doses of carvedilol or other beta-blockers. To address these obstacles, we studied if an automated telemedicine system named TeleWatch (TW) could facilitate carvedilol titration in outpatients with left ventricular systolic dysfunction. METHODS: Forty-nine patients with New York Heart Association class II and III left ventricular systolic dysfunction, who were tolerating appropriate afterload-reducing therapy and not receiving beta-blockers, were enrolled into a 3-month study. Patients were randomized to have clinic-only (CO) (n = 24) carvedilol titration or titrations which combined clinic visits with TW monitoring (n = 25). All patients were seen in clinic biweekly, and those in the TW group were remotely monitored daily. Using a predefined algorithm, patients in the CO and TW groups were eligible for carvedilol titration on a biweekly or weekly basis, respectively, by physicians blinded to group assignment. RESULTS: There was no statistical difference in the mean final daily dose of carvedilol between the CO and TW groups (39.4 vs 36.2 mg/d, P = .52). Because remote telemedicine titrations were as successful as titrations in the clinic, the time to reach the final dose of carvedilol was significantly shorter in the TW group (33.6 vs 63.7 days, P < .0001). There were 5 serious adverse events in the study, 4 of which were in the TW group (P = .29); however, TW prospectively detected 2 adverse events. CONCLUSIONS: Remote monitoring with an automated telemedicine system can successfully facilitate titration of carvedilol in outpatients with New York Heart Association class II and III congestive heart failure.

Adrenergic beta-Antagonists↗

Attenuation of unfavorable remodeling by exercise training in postinfarction patients with left ventricular dysfunction: results of the Exercise in Left Ventricular Dysfunction (ELVD) trial.

BACKGROUND: Exercise is currently recommended for patients after myocardial infarction; however, the effects of regular exercise on the remodeling process remain to be defined. The aim of this multicenter, randomized study was to investigate whether a long-term physical training program influences left ventricular size and function in postinfarction patients with systolic dysfunction. METHODS AND RESULTS: Consecutive patients with <40% ejection fraction after a first Q-wave myocardial infarction were randomly assigned to a 6-month exercise training program (n=39) or control group (n=38). After 6 months, a significant increase in work capacity was observed only in the training group (from 4.462+/-1.095 to 5.752+/-1.749 kilopond-meters [Kp-m], P<.01), not in the control group (from 4.375+/-1.143 to 4.388+/-1.199 Kp-m), whereas left ventricular volumes had increased in the control group (end-diastolic volume, from 94+/-26 to 99+/-27 mL/m2, P<.01; end-systolic volume, from 62+/-20 to 67+/-23 mL/m2, P<.01) but not in the training group (end-diastolic volume, from 93+/-28 to 92+/-28 mL/m2, P=NS; end-systolic volume, from 61+/-22 to 57+/-23 mL/m2, P=NS). Conversely, ejection fraction had improved in the training group (from 34+/-5% to 38+/-8%, P<.01) but not in the control group (from 34+/-5% to 33+/-7%, P=NS). CONCLUSIONS: In postinfarction patients with systolic dysfunction, long-term exercise training may attenuate the unfavorable remodeling response and even improve ventricular function over time.

Adult↗

Plasma brain natriuretic peptide to detect preclinical ventricular systolic or diastolic dysfunction: a community-based study.

BACKGROUND: Preclinical systolic or diastolic dysfunction is associated with increased morbidity and mortality. We postulated that plasma brain natriuretic peptide (BNP) might serve as a biomarker for preclinical ventricular dysfunction (PCVD) but that the discriminatory values for BNP may vary with age and sex. METHODS AND RESULTS: We measured BNP, systolic and diastolic ventricular function, and clinical parameters in 2042 randomly selected residents of Olmsted County, Minn, aged 45 years or older. For preclinical systolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with more severe (0.82 to 0.92) than any (0.51 to 0.74) systolic dysfunction and were similar in men and women and in younger and older persons. For preclinical diastolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with moderate-to-severe (0.74 to 0.79) than any (0.52 to 0.68) diastolic dysfunction and were similar regardless of age or sex. Optimal discriminatory values of BNP varied with age and sex. Considering the prevalence of preclinical systolic or diastolic dysfunction and the predictive characteristics observed, using BNP to screen for PCVD would necessitate echo in 10% to 40% of those screened, with most confirmatory echocardiograms being negative, and would miss 10% to 60% of those affected. CONCLUSIONS: BNP is a suboptimal screening test for PCVD in the population.

Age Factors↗

Utility of B-type natriuretic peptide in differentiating congestive heart failure from lung disease in pediatric patients with respiratory distress.

Plasma B-type natriuretic peptide (BNP) has been reported to be helpful in differentiating cardiac from pulmonary etiologies of dyspnea in adults. We investigated whether BNP concentration could be applied similarly in children with respiratory distress. BNP levels were measured using a rapid immunoassay in 49 infants and children presenting with acute respiratory distress. The patient's history, symptoms, physical exam, chest x-ray, and an echocardiogram were used to identify patients with congestive heart failure (CHF) from noncardiac causes of respiratory distress. Results are reported as mean+/-SD. Patients with CHF (n = 23) had BNP levels of 693.0+/-501.6 pg/ml, significantly higher than those of the group of patients with lung disease (n = 26), whose BNP was 45.2+/-64.0 pg/ml (p < 0.001). There was no significant difference in age between the two groups (29.7+/-59.3 vs 13.1+/-22.6 months; p = 0.12). A BNP level of 40 pg/ml was 84% accurate in differentiating CHF from pulmonary disease. Fifteen of 23 CHF patients had ventricular volume overload from left-to-right shunting congenital heart defects and 8/23 had left ventricular systolic dysfunction. Age-adjusted comparison of the two subgroups of CHF patients revealed that children with left ventricular systolic dysfunction had significantly higher mean BNP levels than those with left-to-right shunts (1181+/-487 vs 433+/-471 pg/ml, p = 0.0074). We conclude that BNP level is of value in differentiating cardiac from pulmonary causes of respiratory distress in children.

Age Factors↗

Acute positive inotropic intervention: the phosphodiesterase inhibitors.

Phosphodiesterase inhibitors that are selective for cAMP-specific cardiac and vascular PDE III comprise a new group of agents for the treatment of heart failure, which at present are limited to clinical shortterm intravenous use and research uses only. Although both intravenous amrinone and milrinone are FDA approved, only amrinone is available for general clinical use. Selective phosphodiesterase inhibition produces beneficial actions of positive inotropy and peripheral vasodilation that result from increased cardiac and vascular muscle concentrations of intracellular cAMP and ionic calcium. In addition, a positive lusitropic action (enhancement of cardiac relaxation) has been observed. Neither beta-adrenergic agonist activity nor inhibition of the sodium-potassium ATPase is produced by these agents. The magnitude of hemodynamic improvement generally exceeds that of the cardiac glycosides and is comparable with that of intravenous catecholamines such as dobutamine. The different pharmacodynamic profile of the PDE inhibitors is additive to the effects of cardiac glycosides, complementary and synergistic to the actions of catecholamines, and has been shown to have favorable effects on coronary hemodynamics. As a result there is continued enthusiasm for the short-term intravenous use of amrinone and potentially milrinone in the setting of acute heart failure resulting from systolic dysfunction (after myocardial infarction, open heart surgery, or infectious or toxic myocarditis), heart failure resulting from right ventricular systolic dysfunction, and when patients with severe heart failure await cardiac transplantation. Initiation of treatment with an intravenous bolus followed by a maintenance infusion provides prompt increases in stroke volume and cardiac output and simultaneous reductions in right and left ventricular filling pressures and systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗

Altered SR protein expression associated with contractile dysfunction in diabetic rat hearts.

The goal of this study was to examine whether alteration of sarcoplasmic reticulum (SR) protein levels is associated with early-onset diastolic and late-onset systolic dysfunction in streptozotocin (STZ)-induced diabetic rat hearts. Four-week diabetic rat hearts exhibited slow relaxation, whereas 6-wk diabetic rat hearts exhibited slow and depressed contraction. Total phospholamban level was increased, and phosphorylated level was decreased in 4- and 6-wk diabetic rat hearts. Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) protein level was unchanged in 4-wk but decreased in 6-wk diabetic rat hearts. Only the apparent affinity of SR Ca2+ uptake for Ca2+ was decreased in 4-wk diabetic rat hearts, but the apparent affinity and the maximum rate was decreased in 6-wk diabetic rat hearts. Insulin treatment of the diabetic rats normalized SR protein expression and function. It was concluded that an increase in nonphosphorylated phospholamban and a decrease in the apparent affinity of SR Ca2+ pump for Ca2+ are associated with early-onset diastolic dysfunction and decreases in SERCA2 protein level and apparent affinity and maximum velocity of SR Ca2+ pump are associated with late-onset systolic dysfunction in diabetic rats.

Animals↗

Aprotinin pretreatment diminishes postischemic myocardial contractile dysfunction in dogs.

UNLABELLED: We evaluated the effect of aprotinin, administered before the onset of acute regional myocardial ischemia, on reversible contractile dysfunction induced by ischemia and reperfusion in pentobarbital-anesthetized dogs. Animals were randomized to receive either aprotinin 30,000 kallikrein inactivator units (KIU)/kg and 7000 KIU x kg(-1) x hr(-1) (n = 8) or equivalent volumes of 0.9% sodium chloride (n = 7) IV 60 min before a 15-min interruption of circumflex coronary artery blood flow and then reperfusion. There were no intra- or intergroup differences in hemodynamic variables or regional myocardial mechanics (sonomicrometry) before onset of ischemia. Immediately before reperfusion, systolic dysfunction characterized by significantly decreased percent systolic shortening was present in the circumflex coronary artery area of both study groups. After reestablishment of perfusion, aprotinin animals had preserved percent systolic shortening whereas saline animals exhibited regional systolic dysfunction. Regional myocardial contractility as assessed by the slope Mw of the preload recruitable stroke work relation was preserved during reperfusion in animals who received aprotinin but depressed in the control group. We conclude that functional recovery from myocardial ischemia-reperfusion injury at normothermia is improved by IV administration of aprotinin before the onset of acute regional myocardial ischemia in physiologically intact dogs. IMPLICATIONS: Administration of clinically relevant doses of aprotinin IV before the onset of regional myocardial ischemia, in contrast to control conditions, preserved regional systolic function and contractility at baseline values after reestablishment of myocardial perfusion in dogs.

Animals↗