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Melo, P. H.

Publications and source records attributed to Melo, P. H..

2 recordsLinked to original sources
bioRxiv2026

Cardiac unloading via a transvalvular pump prevents arrhythmias following myocardial ischemia / reperfusion by preserving coronary microcirculation and cardiomyocyte nanostructure

Cardiac damage in the aftermath of myocardial ischemia / reperfusion (MI/R) compromises both electrical and mechanical function, predisposing patients to arrhythmia and heart failure. Microvascular obstruction (MVO) is increasingly recognized as a sequela of MI/R and a contributor to proarrhythmic cardiac remodeling. While transvalvular unloading (TVU) using a percutaneously delivered pump is garnering appreciation as a means of limiting infarct size and preserving mechanical function following percutaneous coronary intervention, its benefits for arrhythmia prevention remain unclear. We used a porcine model to test the hypothesis that cardiac unloading prior to and through reperfusion mitigates MVO, preserves cardiomyocyte nanostructure, and alleviates arrhythmias following MI/R. Anesthetized domestic swine undergoing acute ischemia (LAD occlusion, 90 mins) and reperfusion (120 mins) were randomized to TVU (n=5) and no treatment (control; n=6) treatments. Thioflavin-S was infused into the mid-LAD to assess coronary microcirculation and quantify MVO. Arrhythmia burden was assessed by in vivo electrocardiography using 3 lead EKG. Cardiac tissues were preserved for histology and optical microscopy studies. Compared to no treatment controls, TVU hearts evidenced significantly reduced infarct area (48 +/- 5 % vs. 59 +/- 11 % p = 0.03) and MVO (19 +/- 4 % vs. 27 +/- 5% , p = 0.03) normalized to area at risk and a higher myocardial salvage index (52 +/- 5 % vs. 41 +/- 11% p = 0.03). Extensive perivascular edema, and neutrophil infiltration observed in controls was markedly reduced in TVU hearts. Confocal microscopy and spatial pattern analysis revealed significantly mitigated disruption of gap junctions and NaV1.5 dissociation from N-cadherin in TVU hearts compared to controls. Importantly, severity-adjusted arrhythmia burden during reperfusion was significantly lower in TV-P hearts (8+/-8 vs. 12+/-5 episodes lasting greater than 5seconds in controls). Our results demonstrate that TVU effectively prevents arrhythmias during reperfusion by preserving coronary microvasculature and cardiomyocyte nanostructure.

physiology↗
bioRxiv2026

Cold acclimation reprograms hepatic lipid composition toward n-3 HUFAs to uncouple adipose-derived lipid flux from steatosis

While cold exposure drives lipid flux from adipose tissue to the liver, this enhanced inter-organ crosstalk does not result in sustained hepatic steatosis during prolonged acclimation, indicating that factors beyond lipid flux shape metabolic outcome. To interrogate this adaptation, we performed integrated lipidomic and metabolic profiling across tissues and circulating lipoproteins over the course of cold acclimation. We showed that cold acclimation induces systemic reprogramming of lipid quality in mice, characterized by enrichment of n-3 highly unsaturated fatty acids (HUFAs) as a consequence of upregulation of fatty acid desaturases (FADS1 and 2) in the liver and white adipose tissue, thus increasing hepatic n-3/n-6 ratio. Cold-induced increase in n-3 HUFAs cause the suppression of SCD1-mediated desaturation, thus yielding a depletion of monounsaturated fatty acids (MUFAs) in the liver, along with the suppression of lipogenic markers. Notably, this high-HUFA/low-MUFA lipid signature is present in both hepatic free fatty acid and triglyceride pools, indicating that lipid remodeling occurs upstream of triglyceride synthesis. Lipidomic analysis revealed that the remodeled triglycerides are incorporated into very-low-density and intermediate density lipoproteins (VLDL and IDL), thereby propagating hepatic lipid reprogramming to the circulation. Thus, by selectively increasing endogenous n-3 HUFA availability, cold adaptation suppresses hepatic DNL and MUFA-driven triglyceride assembly, buffering lipid accumulation despite sustained fatty acid influx and reshaping systemic lipid distribution with potential cardiometabolic impact.

biochemistry↗