Effect of diltiazem on regional oxygenation of reperfused myocardium

Reperfusion after 2 hr of experimental ischemia results in reduced blood flow to the reperfused region, as well as elevated regional O2 extraction in that region. The aim of the present study was to determine whether diltiazem, administered during reperfusion, can improve regional blood flow and lower O2 extraction in the previously occluded region. In open-chest anesthetized dogs, 2-hr occlusion of the left anterior descending coronary artery was followed by a 4-hr period of reperfusion. In 7 of the 15 animals, diltiazem (0.45 micrograms/kg/min) was infused i.v. during the reperfusion period; this was preceded by a loading dose of 0.18 micrograms/kg 10 min before release. Small artery and vein O2 saturations obtained microspectrophotometrically were combined with regional blood flow measurements using radioactive microspheres to determine regional myocardial O2 consumption. In both groups, coronary occlusion lowered regional flow to a similar level. After a 4-hr reperfusion, flow to the subendocardial region of treated hearts was significantly greater than that to the untreated reperfused myocardium (75.6 +/- 46.4 vs. 40.3 +/- 25.8 ml/min/100 g), and did not differ from the preocclusion level. The subendocardium/subepicardium flow ratio was reversed in occluded and untreated reperfused myocardium (subendocardium flow less than subepicardium flow), but was not reversed in treated reperfused regions. Myocardial oxygen extraction was 11.0 +/- 2.4 ml of O2/100 ml of blood in the untreated reperfused subendocardium, and was significantly decreased to 8.5 +/- 0.9 ml of O2/100 ml in the treated subendocardium. The proportion of individual veins having O2 saturations below 25% was significantly reduced by diltiazem treatment from 45.2 to 22.7%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental Evaluation of the Elastic Determinants of Myocardial Function in vivo

Shortening of myocardial fibers occurs following force development in those fibers. The extent, speed and timing of shortening are determined by kinetics and extent of force. However, shortening is also influenced by the elastance/viscosity of the muscle tissue, because that determines the coupling between force and shortening. In the in vivo dog heart, we estimated that coupling by measuring local myocardial force and fiber shortening independently under various conditions. We determined the effect of positive and negative inotropy (by intracoronary injection of dobutamine and acetylcholine, respectively), and of dysfunctional contraction produced by local ischemia/reperfusion and BDM. Under baseline and both positive and negative intropy, most shortening occurred during systole, and dobutamine increased the proportion of total shortening in early systole from 45.8 ± 8.5% to 74.9 ± 9.6%. During reperfusion following ischemia, shortening in early systole was markedly reduced to 16.5 ± 2.9; BDM caused a similar reduction to 16.5 ± 8.1. Most of the shortening occurred during early diastole (53.0 ± 6.8 for reperfusion, and 54.0 ± 10.3 for BDM). These effects were all reversible. It is concluded that energetic efficiency is greatly affected by the elastic properties coupling force and shortening. Thus appropriate analysis of muscle function must take into account the changeable elastic properties of the tissue—both force and shortening, and their interaction must be considered.     

Regional asynchrony of segmental contraction may explain the “oxygen consumption paradox” in stunned myocardium

Summary Despite apparently depressed function, stunned myocardium maintains oxygen consumption and has the capacity to increase contractility with inotropic stimulation. We hypothesized that during stunning, O₂ demand is maintained because regional segment work is performed, but is asynchronous with global left ventricular contraction, and that inotropic stimulation would restore regional work and synchrony. Thirteen open-chest anesthetized dogs were subjected to three left anterior descending (LAD) coronary artery occlusions (10 min) and reperfusions (15 min) to produce regional myocardial stunning. Segment shortening and force development were measured independently and simultaneously in the LAD (experimental) region and circumflex (control) regions. Regional myocardial work was calculated as the integrated product of instantaneous force and shortening, during two periods: 1) over the entire cardiac cycle (Positive Work), and 2) limited to the systolic portion of the cardiac cycle (Systolic Work). Regional myocardial O₂ consumption (MVO₂) was calculated from regional blood flow (radiolabeled microspheres) and O₂ saturation data (microspectrophotometry). Occlusion of the LAD produced a delay in onset of segment shortening in the ischemic region, but not in regional force development. A time delay of 67–81 ms persisted through the three stages of occlusions and reperfusion. Systolic regional work was depressed to a greater extent (924±182 to 149±118 g*mm*min^–1) than total positive regional work (1437±337 to 857±174 g*mm*min^–1). Regional subepicardial MVO₂ in the stunned region was not different than in the control region (7.3±1.5 vs. 6.9±1.4 ml O₂*min^–1*100 g^–1). Local infusion of isoproterenol reversed the delay in regional shortening from 73±7 to 21±8 ms, thereby augmenting systolic work (298%) more than positive work (60%), without a significant increase in MVO₂ (7.3±1.5 to 10.5±3.2 ml O₂*min^–1*100 g^–1). It is concluded that myocardial stunning decreases regional systolic work due to regional mechanical asynchrony, while MVO₂ is used supported total positive work which was not significantly reduced. Isoproterenol restores regional work by restoring synchrony, without greatly affecting regional MVO₂.This study was supported in part by a research grant from the Schulz Foundation and USPHS grant HL40320.     

Relationship between adenylate cyclase activity and regional myocardial energetics in experimental left ventricular hypertrophy

The aim of this study was to examine the responsiveness of the hypertrophied left ventricle to beta-adrenergic stimulation in a pressure overload model produced by valvular aortic stenosis and characterized by reduced beta-adrenoceptor number. The study was designed to correlate changes in global and regional cardiac work and energetics in response to isoproterenol with adenylate cyclase activity. Eleven anesthetized dogs with left ventricular hypertrophy and 11 controls were studied at rest and during 0.5 and 1.0 micrograms/kg/min isoproterenol infusion. We measured regional work from segment length and force changes with ultrasonic dimension crystals and miniature force gauges in addition to arterial and left ventricular blood pressure and cardiac output. Regional myocardial oxygen consumption was calculated from O2 extraction using microspectrophotometry and blood flow using radioactively labeled microspheres. Adenylate cyclase activity was assayed at baseline and after stimulation with forskolin. Isoproterenol significantly increased heart rate, dP/dtmax, cardiac output, and external work to similar levels in control and hypertrophied animals. Similarly, regional work increased from 463 +/- 115 to 995 +/- 584 g x mm/min for controls and from 392 +/- 156 to 1175 +/- 577 for hypertrophied dogs with high dose isoproterenol. Regional O2 consumption also increased to similar levels (20.3 +/- 14.7 vs 16.2 +/- 6.3 ml O2/min/100 g) in both groups. Adenylate cyclase activity was lower in hypertrophy at baseline (23.9 +/- 7.3 vs 62.9 +/- 14.2 pM/min/mg protein for controls), but was the same as for controls with forskolin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The impact of past COVID-19 infection on pregnancy rates in frozen embryo transfer cycles

Journal of Assisted Reproduction and Genetics - To study the effect of SARS-CoV-2 infection on pregnancy rates in frozen embryo transfer (FET) cycles. A retrospective cohort study including women...     

Early prediction of encephalopathic transformation in children with benign epilepsy with centro-temporal spikes

BackgroundMost children with Benign epilepsy with centro-temporal spikes (BECTS) undergo remission during late adolescence and do not require treatment. In a small group of patients, the condition may evolve to encephalopathic syndromes including epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), or Landau-Kleffner Syndrome (LKS). Development of prediction models for early identification of at-risk children is of utmost importance.AimTo develop a predictive model of encephalopathic transformation using data-driven approaches, reveal complex interactions to identify potential risk factors.MethodsData were collected from a cohort of 91 patients diagnosed with BECTS treated between the years 2005–2017 at a pediatric neurology institute. Data on the initial presentation was collected based on a novel BECTS ontology and used to discover potential risk factors and to build a predictive model. Statistical and machine learning methods were compared.ResultsA subgroup of 18 children had encephalopathic transformation. The least absolute shrinkage and selection operator (LASSO) regression Model with Elastic Net was able to successfully detect children with ECSWS or LKS. Sensitivity and specificity were 0.83 and 0.44. The most notable risk factors were fronto-temporal and temporo-parietal localization of epileptic foci, semiology of seizure involving dysarthria or somatosensory auras.ConclusionNovel prediction model for early identification of patients with BECTS at risk for ECSWS or LKS. This model can be used as a screening tool and assist physicians to consider special management for children predicted at high-risk. Clinical application of machine learning methods opens new frontiers of personalized patient care and treatment.