Improvement In Myocardial Performance Research Articles

Cardiovascular Effects of Stimulators of Soluble Guanylate Cyclase Administration: A Meta-analysis of Randomized Controlled Trials.

Heart failure (HF) is one of the main causes of cardiovascular mortality in the western world. Despite great advances in treatment, recurrence and mortality rates remain high. Soluble guanylate cyclase is an enzyme which, by producing cGMP, is responsible for the effects of vasodilation, reduction of cardiac pre- and after-load and, therefore, the improvement of myocardial performance. Thus, a new therapeutic strategy is represented by the stimulators of soluble guanylate cyclase (sGCs). The aim of this meta-analysis was to analyze the effects deriving from the administration of sGCs, in subjects affected by HF. A systematic literature search of Medline, SCOPUS, and Google Scholar was conducted up to December 2022 to identify RCTs assessing the cardiovascular effects, as NT-pro-BNP values and ejection fraction (EF), and all-cause mortality, of the sGCs. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics. The results obtained documented a statistically significant improvement in NT-proBNP values (SMD: - 0.258; 95% CI: - 0.398, - 0.118; p < 0.001) and EF (WMD: 0.948; 95% CI: 0.485, 1.411; p < 0.001) in subjects treated with sGCs; however, no significant change was found in the all-cause mortality rate (RR 0.96; 95% CI 0.868 to 1.072; I2, p = 0). The sGCs represent a valid therapeutic option in subjects suffering from HF, leading to an improvement in cardiac performance.

Results of a phase I/II multi-center investigation of udenafil in adolescents after fontan palliation

The Fontan operation results in a circulation that is dependent on low pulmonary vascular resistance to maintain an adequate cardiac output. Medical therapies that lower pulmonary vascular resistance may augment cardiac output and improve long-term outcomes. This phase I/II clinical trial conducted by the Pediatric Heart Network was designed to evaluate short-term safety, pharmacokinetics (PK), and preliminary efficacy of udenafil in adolescents following Fontan. A 5-day dose-escalation trial was conducted in five study cohorts of six subjects each (37.5, 87.5, and 125 mg daily, 37.5 and 87.5 mg by mouth twice daily). A control cohort with 6 subjects underwent exercise testing only. Adverse events (AEs) were recorded, PK samples were collected on study days six through eight, and clinical testing was performed at baseline and day five. The trial enrolled 36 subjects; mean age 15.8 years (58% male). There were no significant differences in subject characteristics between cohorts. No drug-related serious AEs were reported during the study period; 24 subjects had AEs possibly or probably related to study drug. Headache was the most common AE, occurring in 20 of 30 subjects. The 87.5 mg bid cohort was well tolerated, achieved the highest maximal concentration (506 ng/mL) and the highest average concentration over the dosing interval (279 ng/mL), and was associated with a suggestion of improvement in myocardial performance. Exercise performance did not improve in any of the dosing cohorts. Udenafil was well-tolerated at all dosing levels. The 87.5 mg bid cohort achieved the highest plasma drug level and was associated with a suggestion of improvement in myocardial performance. These data suggest that the 87.5 mg bid regimen may be the most appropriate for a Phase III clinical trial.

Exosomal clusterin, identified in the pericardial fluid, improves myocardial performance following MI through epicardial activation, enhanced arteriogenesis and reduced apoptosis

BackgroundWe recently demonstrated that epicardial progenitor cells participate in the regenerative response to myocardial infarction (MI) and factors released in the pericardial fluid (PF) may play a key role in this process. Exosomes are secreted nanovesicles of endocytic origin, identified in most body fluids, which may contain molecules able to modulate a variety of cell functions. Here, we investigated whether exosomes are present in the PF and their potential role in cardiac repair. Methods and resultsEarly gene expression studies in 3day-infarcted mouse hearts showed that PF induces epithelial-to-mesenchymal transition (EMT) in epicardial cells. Exosomes were identified in PFs from non-infarcted patients (PFC) and patients with acute MI (PFMI). A shotgun proteomics analysis identified clusterin in exosomes isolated from PFMI but not from PFC. Notably, clusterin has a protective effect on cardiomyocytes after acute MI in vivo and is an important mediator of TGFβ-induced. Clusterin addition to the pericardial sac determined an increase in epicardial cells expressing the EMT marker α-SMA and, interestingly, an increase in the number of epicardial cells ckit+/α-SMA+, 7days following MI. Importantly, clusterin treatment enhanced arteriolar length density and lowered apoptotic rates in the peri-infarct area. Hemodynamic studies demonstrated an improvement in cardiac function in clusterin-treated compared to untreated infarcted hearts. ConclusionsExosomes are present and detectable in the PFs. Clusterin was identified in PFMI-exosomes and might account for an improvement in myocardial performance following MI through a framework including EMT-mediated epicardial activation, arteriogenesis and reduced cardiomyocyte apoptosis.

Mineralocorticoid receptor blockade prevents Western diet-induced diastolic dysfunction in female mice.

Overnutrition/obesity predisposes individuals, particularly women, to diastolic dysfunction (DD), an independent predictor of future cardiovascular disease. We examined whether low-dose spironolactone (Sp) prevents DD associated with consumption of a Western Diet (WD) high in fat, fructose, and sucrose. Female C57BL6J mice were fed a WD with or without Sp (1 mg·kg(-1)·day(-1)). After 4 mo on the WD, mice exhibited increased body weight and visceral fat, but similar blood pressures, compared with control diet-fed mice. Sp prevented the development of WD-induced DD, as indicated by decreased isovolumic relaxation time and an improvement in myocardial performance (<Tei index) and septal annular velocity (<E'-to-A' ratio), as assessed by echocardiography, as well as decreased diastolic relaxation time/increased diastolic initial filling rate, as assessed by MRI. The relationship between passive sarcomere length of cardiac myocytes and ventricular pressure was monitored using di-8-ANEPPS staining of the t-tubule network in hearts ex vivo. Sp administration led to longer sarcomere lengths at each pressure indicative of improved ventricular compliance in WD-fed mice. Sp also prevented left ventricular hypertrophy, interstitial fibrosis, and oxidative stress. Sp prevented the WD-induced increased expression of myocardial proinflammatory M1 macrophage markers monocyte chemoattractant protein-1 and CD11c and increased the expression of the anti-inflammatory M2 macrophage marker CD206. These findings demonstrate that WD-induced DD is associated with increased oxidant stress, fibrosis, and immune dysregulation. Mineralocorticoid receptor antagonism enhanced M2 macrophage polarization and ameliorated oxidant stress and fibrosis. This work supports a novel blood pressure-independent effect of MR antagonism as a strategy to prevent diet-induced DD in women. Mineralocorticoid antagonism; low-dose spironolactone; aldosterone;high-fat diet; high-fructose diet; oxidative stress; inflammation; cardiac hypertrophy; myocardial compliance.

Chronic Dipeptidyl Peptidase-4 Inhibition With Sitagliptin Is Associated With Sustained Protection Against Ischemic Left Ventricular Dysfunction in a Pilot Study of Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

The incretin hormone, glucagon-like peptide-1, promotes myocardial glucose uptake and may improve myocardial tolerance to ischemia. Endogenous glucagon-like peptide-1 (7-36) is augmented by pharmacological inhibition of dipeptidyl peptidase-4. We investigated whether chronic dipeptidyl peptidase-4 inhibition by sitagliptin protected against ischemic left ventricular dysfunction during dobutamine stress in patients with type 2 diabetes mellitus and coronary artery disease. A total of 19 patients with type 2 diabetes mellitus underwent dobutamine stress echocardiography with tissue Doppler imaging on 2 separate occasions: the first (control) while receiving oral hypoglycemic agents, and the second after the addition of sitagliptin (100 mg once daily) for ≈4 weeks. Sitagliptin increased plasma glucagon-like peptide-1 (7-36) levels and, at peak stress, enhanced both global (ejection fraction, 70.5±7.0 versus 65.7±8.0%; P<0.0001; mitral annular systolic velocity, 11.7±2.6 versus 10.9±2.3 cm/s; P=0.01) and regional left ventricular function, assessed by peak systolic velocity and strain rate in 12 paired, nonapical segments. This was predominantly because of a cardioprotective effect on ischemic segments (strain rate in ischemic segments, -2.27±0.65 versus -1.98±0.58 s(-1); P=0.001), whereas no effect was seen in nonischemic segments (-2.19±0.48 versus -2.18±0.54 s(-1); P=0.87). At 30 minutes recovery, dipeptidyl peptidase-4 inhibition mitigated the postischemic stunning seen in the control scan. The addition of dipeptidyl peptidase-4 inhibitor therapy with sitagliptin to the treatment regime of patients with type 2 diabetes mellitus and coronary artery disease is associated with a sustained improvement in myocardial performance during dobutamine stress and a reduction in postischemic stunning. URL: http://www.isrctn.org. Unique identifier ISRCTN61646154.

Carvedilol Versus Metoprolol Succinate Do Not Differ in Determining Improvement in Myocardial Performance, Reverse Remodeling, and Long-Term Outcomes in Chronic Systolic Heart Failure

Carvedilol Versus Metoprolol Succinate Do Not Differ in Determining Improvement in Myocardial Performance, Reverse Remodeling, and Long-Term Outcomes in Chronic Systolic Heart Failure

Levosimendan reduces plasma cell-free DNA levels in patients with ischemic cardiomyopathy

Heart failure (HF) is a condition associated with the apoptosis and cell death of both cardiac myocytes and cardiac non-myocytes. DNA fragments released from programmed cell death or acute cellular injury are the main sources of disease-associated elevation of cell-free (cf) DNA. We hypothesized that cfDNA could be a relevant marker of cardiac apoptosis in HF patients that could be affected by the improvement of myocardial performance. To test our hypothesis, we measured plasma cfDNA in 19 patients with ischemic HF and severe left ventricular (LV) systolic dysfunction before and 12 h after completion of levosimendan infusion. Echocardiographic and biochemical markers of LV diastolic pressure and LV systolic function were also assessed. In accordance with previous observations levosimendan improved echocardiographic and biochemical indices of LV function. Plasma cfDNA was significantly reduced in HF patients post-levosimendan treatment (median: 89.4, interquartile range: 87.1 to median: 25.9, interquartile range: 12.3, P = 0.028). Notably, in 15/19 patients there was a reduction in cfDNA levels post-levosimendan infusion; while in 12/19 patients, a more than 50% reduction in plasma cfDNA was observed. Since cfDNA is a marker of tissue injury and apoptosis these results indicate that improvement of LV function has a potential impact on cell preservation and survival. Further studies are needed to substantiate our promising results regarding the role of plasma cfDNA as a marker of HF.

BNP as marker of heart dysfunction in patients with liver cirrhosis

Patients with liver cirrhosis suffer various degrees of cardiac dysfunction which may be crucial in determining the outcome of surgery. The aim of this study was to determine the role of natriuretic peptides on the assessment of cardiac dysfunction in patients with liver cirrhosis. Prospective longitudinal study of 30 patients with hepatic cirrhosis. Severity of disease was assessed according to the Child-Turcotte-Pugh and Model for End Stage Liver Disease (MELD) scores. Cardiac function was assessed using endocrine markers [atrial natriuretic peptide-brain natriuretic peptide (BNP)] and isotopic ventriculography at baseline and after stimulation with dobutamine. The ejection fraction was higher in patients with Child A+B and MELD less than 18 than in patients with advanced liver disease. A significant correlation between BNP plasma levels and MELD values was observed. Dobutamine induced a marked improvement in myocardial performance associated to a decrease in BNP levels. Multivariate analysis showed that BNP has prognostic value as a marker of cardiac ejection fraction. Patients whose baseline BNP concentrations were more than 70 pg/ml had an ejection fraction of around 45%. This study has shown that increased baseline BNP concentrations may be regarded together with high Child and MELD scores, as the critical cardiac dysfunction threshold in cirrhotic patients.

Ras inhibition attenuates myocardial ischemia–reperfusion injury

Myocardial injury, developed after a period of ischemia/reperfusion (I/R) results in the destruction of functional heart tissue, this being replaced by scar tissue. Intracellular signaling pathways mediating cardiomyocyte death are partially understood and involve the activation of Ras. p38–MAPK, JNK and Mst-1 are downstream effectors of Ras protein. We hypothesized that S-farnesylthiosalicylic acid (FTS), a synthetic small molecule that detaches Ras from the inner cell membrane, consequently inhibiting Ras activity, reduces I/R myocardial injury in vitro and in vivo. Wistar rat hearts were isolated, mounted on the Langendorff apparatus and subjected to ischemia (30 min, 37 °C) and reperfusion. During the reperfusion period, the hearts were perfused with FTS (1 μM) solution or control buffer. Left anterior descending (LAD) ligation and subsequent reperfusion was performed in two groups of Wistar rats. Rats received 5 mg/kg FTS or PBS according to two protocols: (A) FTS or PBS were administered daily 7 days prior, immediately before and 14 days (every other day) after LAD occlusion or (B) every other day for 14 days post-I/R. Hearts from FTS-treated rats (Langendorff) and FTS-treated rats (protocol A) showed a significant improvement in myocardial performance and smaller scar tissue compared with the PBS group. Infarct size in the FTS-treated group was 12.7 ± 2% vs. 23.7 ± 4% in the PBS-treated ( in vitro) group and 17.3 ± 2.5% vs. 36 ± 7% compared with control I/R rats ( in vivo) p < 0.05. These effects may be associated with the down regulation of JNK as a short-term effector and with Mst-1 in the long-term remodeling process.

Early experience with Levosimendan in children with ventricular dysfunction*

To describe our preliminary experience with Levosimendan, a new calcium-sensitizing agent in critically unwell infants and children with severe heart failure. Retrospective cohort analysis. Pediatric intensive care unit. Fifteen children aged 7 days to 18 yrs (median age 38 months) with severe myocardial dysfunction secondary to end-stage heart failure, or acute heart failure, who were inotrope-dependent (requiring at least one catecholamine). A single dose (bolus and intravenous infusion over 24-48 hrs) of Levosimendan was given under continuous hemodynamic monitoring in our intensive care unit. Eleven children received a single dose, three children received two doses, and one child received four doses. Echocardiographic assessments of ventricular function were made before and 3-5 days after Levosimendan infusion. Heart rate, systolic pressure, diastolic pressure, mean blood pressure, and central venous pressure were unchanged during and after Levosimendan. Levosimendan allowed for discontinuation of catecholamines in ten patients and a dose reduction in three. The dose of dobutamine was reduced from 6.4 microg/kg/min pre-Levosimendan to 1.8 microg/kg/min on day 5 (p < .01). Ejection fraction for the group as a whole improved from 29.8% to 40.5% (p = .015); this did not increase significantly in patients with end-stage heart failure but increased by 63% in the children with acute heart failure. Levosimendan can be safely administered to infants and children with severe heart failure. Levosimendan allowed for substantial reduction in catecholamine infusions in children with end-stage or acute heart failure and also produced an objective improvement in myocardial performance in children with acute heart failure.

Cellular cardiomyoplasty: a new therapeutic approach for regenerating the myocardium.

One of the most promising new therapeutic techniques for the augmentation and regeneration of the myocardium is cellular cardiomyoplasty. Reports from animal and clinical investigations indicate that the transplant of different cell types, such as autologous skeletal myoblasts and adult stem cells, into injured myocardium results in the generation of new cardiac myocytes and improvement in myocardial performance. Although there is no consensus with regard to the best cell type to transplant or the extent of myocardial renewal and regeneration, the technique of cardiac cellular myoplasty may become one of the most important advancements in the treatment of cardiovascular diseases such as myocardial infarction and heart failure.

Early remodelling of left ventricle and improvement of myocardial performance in patients after percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy

Background: Percutaneous transluminal septal myocardial ablation (PTSMA) reduces left ventricular outflow (LVOT) gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM) and leads to symptomatic improvement. Effects of PTSMA on left ventricular performance are currently unknown. The purpose of this study was to evaluate changes in the left ventricular performance using Doppler index of myocardial performance (sum of isovolumic contractile and relaxation times divided by left ventricular ejection time) and left ventricular remodelling after PTSMA for HOCM. Methods: Twenty-five patients with symptomatic HOCM underwent echocardiography-guided PTSMA procedure. Clinical and echocardiographic data were collected at baseline and 3 months after PTSMA. Results: PTSMA procedures were uneventful, in one patient (4%), pacemaker implantation was needed for sustained complete heart block after the procedure. At 3-month follow-up, the maximal LVOT gradient decreased from 68±39 to 18.6±12 mmHg ( P<0.001), the provoked maximal LVOT gradient decreased from 128.8±59 to 25±21.4 mmHg ( P<0.001), and basal septal thickness decreased from 21.7±4 to 15.2±3 mm ( P<0.001). The improvement of the index of myocardial performance (from 0.65±7 to 0.56±11; P<0.001) was associated with neither significant change in left ventricular ejection fraction nor left ventricular ejection time. There was no significant difference in the left ventricular dimension at baseline and at follow-up. All patients reported a significant improvement in symptoms at follow-up, the mean NYHA class decreased from 2.6±0.7 to 1.4±0.7 ( P<0.001), and the number of patients suffering from episodes of syncope or attacks of dizziness decreased from 13 to two during the 3-month follow-up. Conclusions: PTSMA is a safe, effective and reproducible method in the treatment of highly symptomatic patients with HOCM. This procedure results in a significant relief of symptoms associated with decrease in LVOT gradient and thickness of basal interventricular septum. Positive changes in Doppler IMP suggest possible improvement of left ventricular function.

Cardiac performance during vasopressin infusion in postcardiotomy shock

Arginine-vasopressin (AVP) might be a potent vasopressor agent in catecholamine-resistant postcardiotomy shock. However, its use remains experimental because of considerations about deleterious effects on the heart. We report on the effects of continuous AVP-infusion on cardiac performance, biomarkers of myocardial ischemia, and systemic hemodynamics in catecholamine-resistant postcardiotomy shock. Retrospective study. Twenty-one-bed general and surgical intensive care unit. Forty-one patients with catecholamine-resistant postcardiotomy shock. Continuous infusion of AVP. Heart rate (HR), heart rhythm, mean arterial pressure (MAP), central venous pressure, mean pulmonary arterial pressure, cardiac index (CI), stroke volume index (SVI), left ventricular stroke work index (LVSWI), systemic vascular resistance (SVR) as well as milrinone and norepinephrine requirements were collected before and 1, 4, 12, 24, and 48 h after start of AVP infusion. Creatine kinase MB and troponin-I serum concentrations were measured daily. During AVP administration we observed a significant decrease in HR (-14.8%), milrinone (-17.5%), and norepinephrine requirements (-54.9%) as well as biomarkers of cardiac ischemia and a significant increase in LVSWI (+46.2%), MAP (+41.8%) and SVR (+60%). CI and SVI remained unchanged. Forty-five percent of postoperative new-onset tachyarrhythmias (TA) converted into sinus rhythm during AVP infusion. AVP was devoid of adverse effects on the heart in these patients with catecholamine-resistant postcardiotomy shock. The significant reduction in HR, vasopressor, and inotropic support suggest a substantial improvement in myocardial performance. These findings are supported by a significant decrease of cardiac enzymes and cardioversion of TA into sinus rhythm in 45.5% of patients with new-onset TA.

Late preconditioning elicited by activation of adenosine A(3) receptor in heart: role of NF- kappa B, iNOS and mitochondrial K(ATP) channel.

Activation of adenosine A(3) receptor (A(3)AR) protects against ischemia/reperfusion injury in the heart. However, the downstream signaling mechanisms leading to its delayed anti-ischemic effects remain unclear. We hypothesized that A(3)AR stimulation protects the heart via activation of nuclear transcription factor kappa B (NF-kappa B) and synthesis of inducible nitric oxide synthase (iNOS). Mice were treated with selective A(3)AR agonist, N(6)-(3-iodobenzyl) adenosine-5;-N-methyluronamide (IB-MECA). Twenty-four h later, hearts were perfused in Langendorff mode and subjected to 30 min of global ischemia and 30 min of reperfusion. IB-MECA caused post-ischemic reduction in necrosis and improvement in myocardial performance which was abolished by A(3)AR antagonist, MRS1191. Electrophoretic mobility shift assay demonstrated increased NF-kappa B binding in nuclear extracts following A(3)AR stimulation, which was diminished by MRS1191 and NF-kappa B inhibitor, pyrrolidinediethyldithiocarbamate (PDTC). The cardioprotection was abrogated by PDTC and targeted ablation of p50 subunit of NF-kappa B in mice. The inhibition of iNOS with S-methylisothiourea and targeted disruption of the iNOS gene also abolished the protective effect of A(3)AR stimulation. Expression of iNOS mRNA and NO production were enhanced after 6 and 24 h respectively of IB-MECA treatment. MRS1191 and PDTC blocked IB-MECA induced NO production after A(3)AR stimulation. MitoK(ATP) channel blocker, 5-hydroxydecanoate abolished the protective effect of A(3)AR. For the first time, we have provided direct evidence of an essential role of NF- kappa B activation and iNOS in A(3)AR-induced late preconditioning. Selective activation of A(3)AR with IB-MECA can be used to trigger long-lasting ischemic protection in the heart.

Transmyocardial laser revascularization in ischemic cardiomyopathy

Background In ischemic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤30%), myocardial revascularization by coronary artery surgery has better results than heart transplantation, provided there is sufficient ischemic but viable myocardium. The mode of action of transmyocardial laser revascularization (TMR) is still being debated, but if the procedure induces improved myocardial perfusion it could be a “bridge,” or alternative, to heart transplantation. Methods We retrospectively analyzed 194 patients, who underwent TMR between July 1997 and October 1999. Patients with TMR as an adjunct to coronary artery surgery ( n = 30) and those who did not provide written consent to the procedure ( n = 8) were excluded; 126 patients had normal or moderately reduced left ventricular function, and 30 patients with ischemic cardiomyopathy (LVEF ≤30%) were included. Results After 12 months, the Canadian Cardiovascular Society (CCS) score dropped significantly from 3.6 (3 to 4) to 2.4 (1 to 4) and maximum work load increased significantly from 58 W (25 to 100 W) to 73 W (25 to 120 W). However, thallium score and LVEF did not improve significantly (27% [15% to 30%] to 32% [15% to 45%]). Prior to the TMR procedure, all 30 patients had a “low risk” or “medium risk” of death according to the Aaronson classification. The 30-day, 1-year, and 2-year survival rates were 83%, 50%, and 47%, respectively. Conclusions We conclude that TMR in ischemic cardiomyopathy (LVEF ≤30%) has a perioperative risk comparable to that for heart transplantation, but there is no improvement of myocardial performance or life expectancy. Therefore, TMR cannot be regarded as a “bridge,” or alternative, to transplantation. However, in individual cases with contraindications for transplantation the anti-anginal effect may justify use of the procedure.

Comparison of Functional and Metabolic Assessments in Preservation Techniques for Heart Transplantation

The present study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation using metabolic and functional assessments. In both groups the hearts were initially protected with iso-osmolar potassium Tyers' cardioplegia. The donor hearts of group A were placed in simple hypothermic storage for 5 h. The donor hearts of group B were placed onto a perfusion apparatus for 5 h with perfusion pressure maintained at 28 cm of H2O and a myocardial temperature of 8-10 degrees C. The perfustate consisted of Tyers' solution with the addition of 2 mg/L of mannitol, 12.5 mg/L of glucose, 5 units/L of insulin, and 95% oxygen. The ischemic interval within both groups was 6 h, including orthotoipic transplantation. Investigation was conducted at three time periods: prepreservation (T1) in the donor, and postpreservation (T2) and immediately after loading (T3) in the recipient. Following volume loading for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than .05; stroke index, p less than .05) with no significant change in systemic vascular resistance, systemic blood pressure, and heart rate. There was also significant improvement in myocardial performance (p less than .05) for the hypothermic perfusion group following volume loading. Results of fatty acid turnover using 15-p-iodo (123I)-phenylpentodecanoic acid indicate significantly greater increase in metabolic rate for the perfusion group than for the hypothermic storage group. (p less than .05). This indicates improved metabolic status of the heart treated with the hypothermic perfusion technique. We conclude that a combination of functional and metabolic assessments is a good method for deduction of ischemic-reperfusion injury. We also conclude that hypothermic perfusion is superior to hypothermic storage for in vitro preservation of hearts for heart transplantation.

Improvement in myocardial performance without a decrease in high-energy phosphate metabolites after isoproterenol in Syrian cardiomyopathic hamsters.

To determine the effect of isoproterenol on cardiac energetics and function in an animal preparation of cardiomyopathy, we studied Langendorff perfused hearts from Syrian cardiomyopathic hamsters. High-energy phosphate metabolites (phosphocreatine [PCr], ATP, inorganic phosphate [Pi]) and intracellular pH (pHi) were measured by 31P nuclear magnetic resonance spectroscopy and correlated with left ventricular developed pressure, coronary flow, and O2 consumption before and during a 10(-6)M infusion of isoproterenol. Total intracellular calcium was also determined by atomic absorption spectroscopy with the use of potassium ethylenediamine tetra-acetate cobaltate as a marker for extracellular space. In cardiomyopathic hamsters, isoproterenol infusion increased mean developed pressure by 300% (p less than .005 compared with control; n = 5), O2 consumption eightfold (p less than .0005), and PCr by 40% (p less than .05). PCr/Pi ratio, which is analogous to phosphorylation potential, improved 100% (p = .05). In normal hamsters, isoproterenol infusion resulted in an 83% increase in developed pressure (p less than .001) and a 25% increase in O2 consumption (NS). However, mean PCr and PCr/Pi decreased by 30% and 50%, respectively (p less than .05 for both), during isoproterenol infusion. pHi decreased in normal animals (p less than .01), but tended to improve in diseased animals (NS) during isoproterenol infusion. Freeze-clamp measurements of phosphate metabolites correlated well with the nuclear magnetic resonance data. Intracellular calcium increased from 0.0102 +/- 0.002 to 0.144 +/- 0.030 mumol/ml heart water in normal hamsters during isoproterenol infusion. Cardiomyopathic hamsters had a markedly elevated baseline calcium content of 60.82 +/- 5.85 mumol/ml heart water due to the presence of dystrophic calcification.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity‐Sensing, Rate‐Responsive Pacing: Improvement in Myocardial Performance with Exercise

A sensor that detects body activity by low frequency sonic impulses has been incorporated in a pacemaker so that body activity may be translated to an increased pacing rate in response to exercise. The pacemaker is designed for patients who may benefit from an increased cardiac output mediated by an increased heart rate during exercise. Following permanent pacemaker implantation, six patients (mean age 69 years) entered a single blind, randomized, crossover trial for comparison of activity-sensing, rate-responsive pacing (A) to fixed rate demand pacing (D). Ventricular function was assessed by gated radionuclide ventriculography at rest and at exercise, while exercise capacity was assessed by treadmill performance, along with measurements of oxygen consumption and carbon dioxide production. Total treadmill duration and maximum oxygen consumption were similar in the two pacing modes (A = 284 +/- 244 s, 13.4 +/- 3.4 ml O2/min/kg; D = 256 +/- 250 s, 11.7 +/- 3.7 ml O2/min/kg). Anaerobic threshold, however, was significantly improved (A = 266 +/- 199 s, (p less than .05), 13.0 +/- 2.2 ml O2/min/kg (p less than .01); D = 231 +/- 208 s, 10.8 +/- 2.3 ml O2/min/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

The haemodynamic responses to incremental doses of intravenous nitroglycerin in left ventricular failure.

The effects of incremental dose infusions of nitroglycerin, 10-160 micrograms/min, on pulmonary capillary wedge pressure and other haemodynamic variables have been studied in patients with left ventricular failure. Intravenous (IV) nitroglycerin caused a dose-related improvement in myocardial performance, with significant reductions in the raised pulmonary capillary wedge pressure and systemic vascular resistance. At the lowest dose of infusion only the venodilator action of nitroglycerin was apparent. From 40-160 micrograms/min the associated arteriolar dilatation was associated with a consistent improvement in myocardial performance.

Atrial pacing in coronary artery disease, including preinfarction angina and postoperative studies

Right atrial pacing studies were performed in 58 patients with coronary artery disease and in 15 normal subjects. Angina pectoris was induced in 58 percent of patients with coronary artery disease at an average heart rate of 129 ± 3 beats/min; ischemic S-T segment depression was noted in 63 percent of such patients experiencing angina pectoris and in 31 percent of those without angina. The greater the severity of coronary artery disease, the more frequent the pacing-induced angina. The main hemodynamic difference between the normal subject and the patient with coronary artery disease was the failure of the left ventricular end-diastolic pressure to decrease during pacing in the latter. Pacing ventricular function curves were abnormal in 60 percent of patients with coronary artery disease in the absence of angina pectoris and abnormal in 90 percent during induced chest pain. Pacing studies were safely performed in 8 patients with unstable angina pectoris, with angina induced by pacing in 7. No significant hemodynamic differences were noted between these patients and those with stable coronary artery disease. Significant postoperative hemodynamic abnormalities were noted in 9 patients; preoperative and postoperative studies indicated little improvement in myocardial performance after aortocoronary arteryvein bypass surgery.