Publications by authors named "Peter R Pellegrino"

Among patients undergoing surgical oncologic operations, patients in low- and middle-income countries are at particularly high risk for inadequate perioperative analgesia. This article reviews some of the guiding pillars of pain management for cancer surgery, including use of regional analgesia and acute pain service consultation, multimodal adjunctive analgesia, and judicious opioid use while presenting data on international disparities for each pillar and proposing strategies to address these inequities.

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Cardiorenal syndrome type 2 (CRS2) is defined as a chronic cardiovascular disease, usually chronic heart failure (CHF), resulting in chronic kidney disease. We hypothesized that the cardiac spinal afferent reflex (CSAR) plays a critical role in the development of CRS2. Our data suggest that cardiac afferent ablation by resiniferatoxin not only improves cardiac function but also benefits the kidneys and increases long-term survival in the myocardial infarction model of CHF.

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Introduction: A systematic analysis of clinical trials was performed in order to assess the effectiveness and risks of bilateral renal denervation (RDN) in patients with chronic heart failure with reduced ejection fraction (HFrEF).

Methods: A systematic review was conducted of all clinical trials exploring the effectiveness of RDN in patients with HF who had reduced (<50%) EF. Primary outcomes were NYHA class, 6-min walk test, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, left ventricular ejection fraction (LVEF) and other cardiac parameters including left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), and left atrium diameter (LAD).

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Renal sympathetic denervation, a potentially revolutionary interventional treatment for hypertension, faces an existential problem due to the inability to confirm successful ablation of the targeted renal sympathetic nerves. Based on the observation that renal sympathetic nerve activity exerts rhythmic, baroreflex-driven, and vasoconstrictive control of the renal vasculature, we developed a novel technique for identifying rhythmic sympathetic vascular control using a time-varying, 2-component Windkessel model of the renal circulation. This technology was tested in 2 different animal models of renal denervation; 10 rabbits underwent chronic, surgical renal denervation, and 9 pigs underwent acute, functional renal denervation via intrathecal administration of ropivacaine.

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Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem.

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Elevated sympathetic tone and activation of the renin-angiotensin system are pathophysiologic hallmarks of hypertension, and the interactions between these systems are particularly deleterious. The importance of Rho kinase as a mediator of the effects of angiotensin-II (AngII) in the periphery is clear, but the role of Rho kinase in sympathoexcitation caused by central AngII is not well established. We hypothesized that AngII mediates its effects in the brain by the activation of the RhoA/Rho kinase pathway.

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Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms.

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Despite significant clinical interest in renal denervation as a therapy, the role of the renal nerves in the physiological regulation of renal blood flow (RBF) remains debated. We hypothesized that the renal nerves physiologically regulate beat-to-beat RBF variability (RBFV). This was tested in chronically instrumented, healthy rabbits that underwent either bilateral surgical renal denervation (DDNx) or a sham denervation procedure (INV).

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The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF).

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Heart rate variability (HRV) is a function of cardiac autonomic tone that is widely used in both clinical and animal studies. In preclinical studies, HRV measures are frequently derived using the arterial pulse waveform from an implanted pressure telemetry device, termed pulse rate variability (PRV), instead of the electrocardiogram signal in accordance with clinical guidelines. The acceptability of PRV as a surrogate for HRV in instrumented animals is unknown.

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A hallmark of chronic heart failure (CHF) is an increased sympathetic tone resulting in autonomic imbalance. Renal denervation (DNx) in CHF patients has resulted in symptomatic improvement, but the protective mechanisms remain unclear. We hypothesized in CHF, unilateral renal DNx would improve cardiac autonomic balance.

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The small GTPase RhoA and its associated kinase ROCKII are involved in vascular smooth muscle cell contraction and endothelial NO synthase mRNA destabilization. Overactivation of the RhoA/ROCKII pathway is implicated in several pathologies, including chronic heart failure (CHF), and may contribute to the enhanced sympathetic outflow seen in CHF as a result of decreased NO availability. Thus, we hypothesized that central ROCKII blockade would improve the sympathovagal imbalance in a pacing rabbit model of CHF in an NO-dependent manner.

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