Journal of cardiovascular pharmacology
-
J. Cardiovasc. Pharmacol. · Feb 2019
Late Phases of Cardioprotection During Remote Ischemic Preconditioning and Adenosine Preconditioning Involve Activation of Neurogenic Pathway.
The role of the neurogenic pathway in early phases of cardioprotection during remote ischemic preconditioning (RIPC) and adenosine preconditioning is reported. ⋯ Apart from the involvement of the neurogenic pathway in the early phases, there is a critical role of the neurogenic pathway in the late phase of cardioprotection during RIPC and adenosine preconditioning.
-
J. Cardiovasc. Pharmacol. · Jul 2018
Meta AnalysisPerioperative Use of Levosimendan Improves Clinical Outcomes in Patients After Cardiac Surgery: A Systematic Review and Meta-Analysis.
Severe postoperative complications can affect cardiac surgery patients. Levosimendan is a novel calcium sensitizer commonly administered after cardiac surgery. However, the patient benefits are controversial. ⋯ Moreover, levosimendan significantly shortened the duration of the intensive care unit stay (weighted mean differences -0.49 day, 95% CI: -0.75 to -0.24, P = 0.0002) and mechanical ventilation use (weighted mean differences -2.30 hours, 95% CI: -3.76 to -0.84, P = 0.002). In conclusion, levosimendan reduced the mortality in patients with low left ventricular ejection fraction and decreased the incidence of acute renal injury and renal replacement therapy use. In addition, it shortened the duration of the intensive care unit stay and mechanical ventilation use.
-
J. Cardiovasc. Pharmacol. · Jul 2018
Comparative StudyComparative Evaluation of Gemcabene and Peroxisome Proliferator-Activated Receptor Ligands in Transcriptional Assays of Peroxisome Proliferator-Activated Receptors: Implication for the Treatment of Hyperlipidemia and Cardiovascular Disease.
Gemcabene, a late-stage clinical candidate, has shown efficacy for LDL-C, non-HDL cholesterol, apoB, triglycerides, and hsCRP reduction, all risk factors for cardiovascular disease. In rodents, gemcabene showed changes in targets, including apoC-III, apoA-I, peroxisomal enzymes, considered regulated through peroxisome proliferator-activated receptor (PPAR) gene activation, suggesting a PPAR-mediated mechanism of action for the observed hypolipidemic effects observed in rodents and humans. In the current study, the gemcabene agonist activity against PPAR subtypes of human, rat, and mouse were compared with known lipid lowering PPAR activators. ⋯ No clear antagonist activity was observed with gemcabene against any PPAR subtypes for all 3 species over a wide range of concentrations. In summary, the transactivation studies rule out gemcabene as a direct agonist or antagonist of PPAR-α, PPAR-γ, and PPAR-δ receptors of these 3 species. These data suggest that the peroxisomal effects observed in rodents and the lipid regulating effects observed in rodents and humans are not related to a direct activation of PPAR receptors by gemcabene.
-
J. Cardiovasc. Pharmacol. · May 2017
Comparative StudyCyclophilin D Modulates the Cardiac Mitochondrial Target of Isoflurane, Sevoflurane, and Desflurane.
Volatile anesthetics are known to limit myocardial ischemia-reperfusion injuries. Mitochondria were shown to be major contributors to cardioprotection. Cyclophilin D (CypD) is one of the main regulators of mitochondria-induced cell death. We compared the effect of isoflurane, sevoflurane, and desflurane in the presence or absence of CypD, to clarify its role in the mechanism of cardioprotection induced by these anesthetics. ⋯ This study showed different effects of isoflurane, sevoflurane, and desflurane on mitochondrial functions and highlighted the implication of CypD in the regulation of adenosine diphosphate consumption and complex I-induced radical oxygen species production.
-
J. Cardiovasc. Pharmacol. · Mar 2017
ReviewHypertension's 3 Dilemmas and 3 Solutions: Pharmacology of the Kidney in Hypertension.
The Hypertension Community has 3 conflicting dilemmas: a goal systolic pressure of 120 mm Hg or less (the SPRINT Trials), 40% of our 60,000,000 hypertensives still sustain blood pressures above 140/90 mm Hg, and our most potent antihypertensive drug minoxidil sits on the sidelines, imprisoned in the Food and Drug Administration's Black Box designation. My solutions to these dilemmas are: (1) review of the facts of our most potent antihypertensive drug minoxidil which is essentially free of toxicity, (2) treatment focus on the fundamental cause of high blood pressure, that is excess dietary sodium and, (3) prevention of, and/or reversal of, the fundamental mechanism of worsening hypertension, arteriolar hypertrophy.