Functional Recovery Of Left Ventricle Research Articles

Lack of Microsomal Prostaglandin E 2 Synthase-1 in Bone Marrow–Derived Myeloid Cells Impairs Left Ventricular Function and Increases Mortality After Acute Myocardial Infarction

Microsomal prostaglandin E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E(2) biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges(-/-) mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges(+/+) mice after myocardial infarction. In this study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the recovery of LV function after coronary ligation. Cardiac structure and function in Ptges(+/+) mice with Ptges(+/+) bone marrow (BM(+/+)) and Ptges(+/+) mice with Ptges(-/-) BM (BM(-/-)) were assessed by morphometric analysis, echocardiography, and invasive hemodynamics before and 7 and 28 days after myocardial infarction. Prostaglandin levels and prostaglandin biosynthetic enzyme gene expression were measured by liquid chromatography-tandem mass spectrometry and real-time polymerase chain reaction, immunoblotting, immunohistochemistry, and immunofluorescence microscopy, respectively. After myocardial infarction, BM(-/-) mice had more LV dilation, worse LV systolic and diastolic function, higher LV end-diastolic pressure, more cardiomyocyte hypertrophy, and higher mortality but similar infarct size and pulmonary edema compared with BM(+/+) mice. BM(-/-) mice also had higher levels of COX-1 protein and more leukocytes in the infarct, but not the viable LV, than BM(+/+) mice. Levels of prostaglandin E(2) were higher in the infarct and viable myocardium of BM(-/-) mice than in BM(+/+) mice. Lack of mPGES-1 in bone marrow-derived leukocytes negatively regulates COX-1 expression, prostaglandin E(2) biosynthesis, and inflammation in the infarct and leads to impaired LV function, adverse LV remodeling, and decreased survival after acute myocardial infarction.

Peripartum cardiomyopathy in Turkey

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricle systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found [1]. Because of relatively low incidence of the disease, the potential racial differences in clinical presentation and outcomes have not been fully understood. Previous reports indicate that the incidence of PPCM vary in different part of the world suggesting a geographical and etnic disparity. Most of the studies have been performed in the USA, Haiti and South Africa. Data is muchmore limited in the rest of the world including European countries. The studies that have been performed were mostly singlecentre caseseries. From the available literature, the incidence of PPCM appears to be around 1 in 1149–4350 in the USA [2–5], 1 in 1000 in South Africa [6–8], and 1 in 300 in Haiti [9,10]. Disappointingly, there are no European studies of the incidence of PPCM in any population. Available data suggest that the prognosis of PPCM also vary geographically. Mortality rates (0%–9.6%) are lowest in the USA [3,11]. However, Modi et al. reported recovery of left ventricle function and survival rates of PPCM patients in the USA similar to those reported from Haiti and South Africa with a mortality rate of 15.9% [12]. Because 87.5% of the patients in this group were African Americans, the authors suggested that race and ethnicity might be responsible for poorer outcomes. In South Africa, case series have demonstrated that mortality rates have slowly improved over time but 6-month and 2-year mortality rates remain at 10 and 28%, respectively [8]. Single centre studies in

Reverse Remodeling With Left Ventricular Assist Devices

Over the last 2 decades, numerous advancements in medical therapies have improved patient outcomes in heart failure (HF). However, a significant number of patients still progress to end-stage HF, in which treatment options are largely limited to cardiac transplantation. As patient demands for transplant continue to exceed the supply of available organs, mechanical assist devices—specifically, the left ventricular assist device (LVAD)—were initially introduced as a bridge to cardiac transplantation. LVADs have 2 important beneficial effects. First, LVADs are placed in parallel to the native left ventricle (LV), causing pressure and volume unloading of the LV. Second, LVADs restore cardiac output and subsequent perfusion to the organs. As a result of these 2 effects, it became evident that some patients had actual improvement in LV function after LVAD placement. The term reverse remodeling was used to describe the improvement in myocardial function that was observed in patients with a seemingly end-stage disease. With reverse remodeling, a new hope for the treatment of HF was born—using LVADs as a bridge to recovery; however, to date, this promise has largely been unrealized. This probably is reflective of the fact that the sequela of mechanical ventricular unloading are quite complex and appear to involve the engagement of competing biological pathways including regression of cardiomyocyte hypertrophy as well as progressive cell atrophy. Although the promise of ventricular recovery still persists, its actualization will await a more comprehensive dissection of these competing biological processes. This review will discuss the beneficial clinical effects of LVAD support as well as review what is known about the cellular and molecular response to mechanical unloading and mechanisms of reverse remodeling. Key research findings have been summarized in the Table. View this table: Table. Summary of Research of LVAD Support on Clinical Effects and the Cellular and Molecular Changes That May Contribute to Reverse …

Effect of atorvastatin on expression of IL-10 and TNF-α mRNA in myocardial ischemia–reperfusion injury in rats

Myocardial ischemia and reperfusion (MI/R) is associated with an intense inflammatory reaction, which may lead to myocyte injury. Because statins protect the myocardium against ischemia–reperfusion injury via a mechanism unrelated to cholesterol lowering, we hypothesized that the protective effect of statins was related to the expression of TNF-alpha (TNF-α) and interleukin-10 (IL-10) mRNA. Seventy-two rats were randomly divided into three groups as follows: sham, I/R and I/R+atorvastatin. Atorvastatin (20mgkg−1day−1) treatment was administered daily via oral gavage to rats for 2, 7 or 14days. Ischemia was induced via a 30-min coronary occlusion. Reperfusion was allowed until 2, 7 or 14days while atorvastatin treatment continued. We measured infarct size, hemodynamics and the plasma levels and the mRNA expression of TNF-α and IL-10 in the three groups. We demonstrated that the up-regulation of expression of both TNF-α mRNA and IL-10 mRNA was associated the increased plasma levels of TNF-α and IL-10 in the ischemic and reperfused myocardium compared with that in the sham group (P<0.01). Atorvastatin treatment prevented ischemia–reperfusion-induced up-regulation of both TNF-α and IL-10 mRNA, and improved left ventricular function (P<0.01). Our findings suggested that atorvastatin may attenuate MI/R and better recovery of left ventricle function following ischemia and reperfusion and IL-10 was not directly likely involved in this protective mechanism.

Predictors of Prognosis in Patients With Peripartum Cardiomyopathy

Obstetric Anesthesia Digest: March 2009 - Volume 29 - Issue 1 - p 42 doi: 10.1097/01.aoa.0000344710.18797.92

Predictors of prognosis in patients with peripartum cardiomyopathy

Objectives: To evaluate the long-term follow-up results of patients with peripartum cardiomyopathy and assess the echocardiographic findings relating to prognosis at time of diagnosis. Methods: Thirty-three patients diagnosed with peripartum cardiomyopathy and hospitalized between 1995 and 2007 were analyzed. Initial echocardiographic data were recorded and long-term clinical status was evaluated. Results: Eight (24%) patients recovered completely, 10 (30%) died, 2 (6%) underwent heart transplants, and 13 (39%) were left with persistent left ventricular dysfunction. Cut-off values for initial left ventricular end-systolic diameter (≤ 5.5 cm) and left ventricular ejection fraction (> 27%) were obtained from patients who had completely recovered. Conclusion: Cut-off values for initial left ventricular ejection fraction of > 27% and left ventricular end-systolic diameter of ≤ 5.5 cm may predict recovery of left ventricle function.

Prenatal Nicotine Exposure Increases Heart Susceptibility to Ischemia/Reperfusion Injury in Adult Offspring

In the present study we tested the hypothesis that prenatal nicotine exposure increases heart susceptibility to ischemia/reperfusion (I/R) injury in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation. Nicotine treatment resulted in a rapid and transient decrease in food-intake and a moderate decrease in maternal body weight gain. Hearts were isolated from adult male and female offspring and subjected to I/R in a Langendorff preparation. Nicotine significantly attenuated left ventricle (LV) developed pressure, heart rate, and coronary flow rate in female but not male hearts at baseline. Additionally, nicotine significantly increased LV infarct size and attenuated postischemic recovery of LV function in both male and female offspring with more pronounced effects in females. In female but not male hearts, nicotine significantly decreased the postischemic coronary flow rate. However, coronary nitric oxide release was decreased in male but not female hearts. Caspase-3, -8, and -9 levels were not significantly changed in either female or male hearts. However, nicotine caused a significant decrease in protein levels of protein kinase (PK) Cepsilon in both male and female hearts and a decrease in PKCdelta levels in female hearts only. Control studies of maternal food restriction showed that a moderate decrease in maternal body weight gain had no effect on female hearts but significantly improved postischemic recovery of LV function in male hearts. The results suggest that prenatal nicotine exposure causes in utero programming of the PKC isozyme gene expression pattern in the developing heart and increases heart susceptibility to I/R injury in adult offspring.

Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats

In this study, the cardioprotective effects of nitric oxide (NO)-aspirin, the nitroderivative of aspirin, were compared with those of aspirin in an anesthetized rat model of myocardial ischemia-reperfusion. Rats were given aspirin or NO-aspirin orally for 7 consecutive days preceding 25 min of myocardial ischemia followed by 48 h of reperfusion (MI/R). Treatment groups included vehicle (Tween 80), aspirin (30 mg.kg(-1).day(-1)), and NO-aspirin (56 mg.kg(-1).day(-1)). NO-aspirin, compared with aspirin, displayed remarkable cardioprotection in rats subjected to MI/R as determined by the mortality rate and infarct size. Mortality rates for vehicle (n = 23), aspirin (n = 22), and NO-aspirin groups (n = 22) were 34.8, 27.3, and 18.2%, respectively. Infarct size of the vehicle group was 44.5 +/- 2.7% of the left ventricle (LV). In contrast, infarct size of the LV decreased in the aspirin- and NO-aspirin-pretreated groups, 36.7 +/- 1.8 and 22.9 +/- 4.3%, respectively (both P < 0.05 compared with vehicle group; P < 0.05, NO-aspirin vs. aspirin ). Moreover, NO-aspirin also improved ischemia-reperfusion-induced myocardial contractile dysfunction on postischemic LV developed pressure. In addition, NO-aspirin downregulated inducible NO synthase (iNOS; 0.37-fold, P < 0.01) and cyclooxygenase-2 (COX-2; 0.61-fold, P < 0.05) gene expression compared with the vehicle group after 48 h of reperfusion. Treatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg), a nonselective NOS inhibitor, aggravated myocardial damage in terms of mortality and infarct size but attenuated effects when coadministered with NO-aspirin. L-NAME administration did not alter the increase in iNOS and COX-2 expression but did reverse the NO-aspirin-induced inhibition of expression of the two genes. The beneficial effects of NO-aspirin appeared to be derived largely from the NO moiety, which attenuated myocardial injury to limit infarct size and better recovery of LV function following ischemia and reperfusion.

Heat Stress Attenuates ATP-Depletion and pH-Decrease During Cardioplegic Arrest

The capacity of heat stress induction to improve myocardial tolerance against ischemia is well known. We investigated cardiac energy metabolism after hsp 72(+)/73(+) induction in isolated perfused neonatal rabbit hearts subjected to prolonged cold cardioplegic ischemia. Hearts from neonatal rabbits were excised, isolated perfused and arrested by 2-h cold cardioplegic ischemia. Rectal temperature of eight neonatal rabbits was raised to 42.0 to 42.5 degrees C for heat shock protein expression in a whole body water bath for 15 min before the onset of arrest. Another set of eight rabbits without hyperthermia pretreatment served as control. Recovery of left ventricle function was assessed by aortic flow, cardiac output, and max dP/dt. Status of high-energy phosphates was measured by (31)phosphorus nuclear magnetic resonance-spectroscopy. Immunoblot analysis revealed clear hsp 72+/73+ induction after a brief period of systemic hyperthermia. Heat stress pretreatment resulted in a better recovery of left ventricular function (aortic flow and cardiac output improvement P < 0.05, max dP/dt P < 0.01) than in controls at 60 min after reperfusion. During ischemia and reperfusion, myocardial energy metabolism was better preserved in hearts after hsp induction as a consequence of increased gamma-, alpha-, and beta-ATP as well as phosphocreatine-values over controls. The ischemia-induced pH-decrease was attenuated. These data contribute to the evidence of heat stress mediated beneficial effects on functional myocardial recovery and improved cardiac energy metabolism after prolonged cold cardioplegic ischemia. More importantly, the attenuation of ischemic pH reduction and better restoration suggest an involvement of mitochondrial membrane potential alterations.

Hyperoxemic perfusion of the left anterior descending coronary artery after primary angioplasty in anterior ST‐elevation myocardial infarction

To assess left ventricle function recovery, ST-segment changes, and enzyme kinetic in ST-elevation myocardial infarction patients treated with intracoronary hyperoxemic perfusion (IHP) after primary percutaneous coronary intervention and compare them with the results obtained in control patients. IHP has been shown to attenuate microvascular reperfusion injury, which may result in poor LV function recovery despite successful primary percutaneous coronary intervention. Twenty seven anterior ST-elevation myocardial infarction patients treated < or = 12 hr after symptom onset by primary percutaneous coronary intervention were subjected to selective IHP into the left anterior descending coronary artery for 90 min. They were compared with 24 anterior ST-elevation myocardial infarction control patients matched in clinical and angiographic characteristics and treated with conventional primary percutaneous coronary intervention. Left ventricular function recovery was evaluated by serial 2D contrast echocardiography. Left anterior descending coronary artery recanalization was successful in all patients. After IHP (100% successful, duration 90 +/- 5.4 min), patients showed a 4.8 +/- 2.2 hr shorter time-to-peak creatine kinase release (P = 0.001), a shorter creatine kinase half-life period (23.4 +/- 8.9 hr vs. 30.5 +/- 5.8 hr, P = 0.006), and a higher rate of complete ST-segment resolution (78% vs. 42%, P = 0.01). A significant improvement of mean left ventricular ejection fraction (from (44 +/- 9)% to (55 +/- 11)%, P < 0.001) and wall motion score index (from 1.77 +/- 0.2 to 1.39 +/- 0.4, P < 0.001) was observed at 3 months in IHP patients only. After successful primary coronary intervention, IHP is associated with significant left ventricular function recovery when compared to conventional treatment. Enzyme kinetic and ST-segment changes suggest faster and more complete microvascular reperfusion and may explain the salutary effects of this new therapy on left ventricular function.

Myocardial Synchronicity: As a Predictor of Left Ventricle Function Recovery in Severe Congestive Heart Failure

Myocardial Synchronicity: As a Predictor of Left Ventricle Function Recovery in Severe Congestive Heart Failure

Assessment of nicorandil therapy in ischemic myocardial injury by using contrast-enhanced and functional MR imaging.

To determine the potential of mesoporphyrin- and gadopentetate dimeglumine-enhanced and functional magnetic resonance (MR) imaging in the assessment of the acute effect of nicorandil on ischemic injury of the myocardium. Spin-echo MR imaging was used to monitor changes in myocardial contrast and function in reperfused myocardial injury. Inversion-recovery echo-planar MR imaging was used to depict the injured region. Myocardial injury in rats was produced by using 30 minutes of coronary occlusion followed by 24 hours reperfusion. Nicorandil (n = 9) was infused during occlusion and early reperfusion. Control animals (n = 11) received no therapy. At 24 hours, after administration of mesoporphyrin and gadopentetate dimeglumine and histochemical staining, the function and size of the injured region of the left ventricle (LV) were determined. A t test was used to compare data between groups of animals, whereas regression and Bland-Altman analyses were used to determine correlation and agreement between MR imaging and histomorphometry, respectively. Treated animals showed reduced infarction size as compared with the control group from 25.6% +/- 7.9 (SD) to 7.9% +/- 6.8 of LV myocardial area (P < .001), as defined with mesoporphyrin-enhanced MR imaging; while the size of the rim increased from 10.8% +/- 10.0 to 16.1% +/- 14.4 (P < .05). The diastolic-midventricular cavity area was smaller in treated animals (15.2 mm(2) +/- 4.3) compared with the control group (28.5 mm(2) +/- 7.9; P < .001). At functional MR imaging, nicorandil improved systolic reduction in LV cavity area (57.5% +/- 17.3) compared with the control group (38.0% +/- 16.0; P < .05) and preserved regional LV wall thickening at the site of injury (12.2% +/- 11.1 in treated group vs 0.3% +/- 8.6 in the control group; P < .05). Contrast material-enhanced MR imaging has the potential to demonstrate reduction in size of ischemically injured myocardium, whereas functional MR imaging demonstrated the recovery of LV function 24 hours after nicorandil therapy.

Discordant effects of nisoldipine on coronary vascular resistance and permeability changes during reflow after ischemia in isolated rabbit hearts

Effects of a low dose (5 n m) of nisoldipine on vascular and ventricular function were assessed in isolated rabbit hearts during 2 h of reperfusion after 40 min of global, zero-flow ischemia. External detection of bolus injections of 125I-BSA and pressure data generated during the experiment provided repeated estimates of albumin permeation and vascular hemodynamics (resistance, vascular volume, and fractional rate of intravascular washout of 125I-BSA (k 01)). In control hearts perfused continuously for 3.5 h, vascular resistance, vascular volume, LVEDP, and k 01 remained constant, while maximum + dP dt and − dP dt increased 25% above baseline values, and estimates of albumin permeation increased 1.7 × baseline. Addition of 5 n m nisoldipine to the perfusate after the baseline period produced sustained decreases in vascular resistance (16% vs mean baseline value) without significantly affecting any other parameter. Postischemic perfusion of hearts increased vascular resistance and vascular volume ∼50% above baseline, decreased k 01 by 25% (intravascular washout of 125I-BSA was prolonged), and increased albumin permeation ∼5 × baseline. While LVEDP remained elevated 3 × baseline, maximum + dP dt and − dP dt recovered 100% of baseline values (75–80% of untreated control values at comparable time points). Addition of 5 n m nisoldipine to the perfusate prior to ischemia prevented the increased vascular resistance during reflow, prevented the decrease in k 01 and the increase in vascular volume, but did not affect the increased albumin permeation and, in general, did not affect the rate of recovery of left ventricle function. These results indicate that a low dose of nisoldipine preserves postischemic coronary vascular hemodynamics, but has little or no effect on the increased vascular leakage of albumin.

"Getting Married"

In the present study we tested the hypothesis that prenatal nicotine exposure increases heart susceptibility to ischemia/reperfusion (I/R) injury in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation. Nicotine treatment resulted in a rapid and transient decrease in food-intake and a moderate decrease in maternal body weight gain. Hearts were isolated from adult male and female offspring and subjected to I/R in a Langendorff preparation. Nicotine significantly attenuated left ventricle (LV) developed pressure, heart rate, and coronary flow rate in female but not male hearts at baseline. Additionally, nicotine significantly increased LV infarct size and attenuated postischemic recovery of LV function in both male and female offspring with more pronounced effects in females. In female but not male hearts, nicotine significantly decreased the postischemic coronary flow rate. However, coronary nitric oxide release was decreased in male but not female hearts. Caspase-3, -8, and -9 levels were not significantly changed in either female or male hearts. However, nicotine caused a significant decrease in protein levels of protein kinase (PK) Cϵ in both male and female hearts and a decrease in PKCδ levels in female hearts only. Control studies of maternal food restriction showed that a moderate decrease in maternal body weight gain had no effect on female hearts but significantly improved postischemic recovery of LV function in male hearts. The results suggest that prenatal nicotine exposure causes in utero programming of the PKC isozyme gene expression pattern in the developing heart and increases heart susceptibility to I/R injury in adult offspring.