Physiological, Pathological and Pharmacological Interactions of Hydrogen Sulphide and Nitric Oxide in the Myocardium of Rats with Left Ventricular Hypertrophy

Left ventricular hypertrophy (LVH) is characterized by increased myocardium thickness due to increased oxidative stress and downregulation of cystathione γ lyase (CSE) endothelial nitric oxide synthase (eNOS). Upregulation of CSE by hydrogen sulphide (H2S) and ENOS by L-arginine can arrest the progression of LVH individually. The present study explored the combined treatment of H2S and NO in the progression of LVH, and demonstrated that the response is due to H2S, NO or formation of either new molecule in physiological, pathological, and pharmacological in vivo settings of LVH. Exogenous administration H2S+NO in LVH significantly reduced (all p < 0.05) systolic blood pressure (SBP) and mean arterial pressure (MAP), LV index, heart index and oxidative stress when compared to the LVH group. There was downregulation of CSE mRNA and eNOS in the heart, and exogenous administration of H2S+NO groups upregulated eNOS MRNA while CSE MRNA remained downregulated in the hearts of the LVH group. Similar trends were observed with concentrations of H2S and NO in the plasma and tissue. It can be concluded that combined treatment of LVH with H2S and NO significantly ameliorate the progression of LVH by attenuating systemic hemodynamic and physical indices, and by decreasing oxidative stress. Molecular expression data in the myocardium of LVH depicts that combined treatment upregulated eNOS/NO while it downregulated CSE/H2S pathways in in vivo settings, and it is always eNOS/NO pathways which play a major role.

Features of the Clinical Course of Arterial Hypotension in Pregnant Women

A study was carried out of women with arterial hypotension against the background of the development of the pathological state of the fetus and newborns born to women living in two different climatic regions of Osh city and in the highlands of Chon-Alay district of Osh region. In the pathogenesis of pregnancy complications caused by arterial hypotension, the leading importance is attached to vascular disorders and microcirculation disorders, leading to systemic hemodynamic changes in the body of a pregnant woman. It was found that in mountainous terrain, arterial hypotension and exogenous hypoxia affect the “mother–placenta–fetus–newborn” system, increasing the load on the respiratory, circulatory and hematopoietic organs of the mother, and also leads to impaired placental function.

Intravital microscopic observation of the microvasculature during hemodialysis in healthy rats

Hemodialysis (HD) provides life-saving treatment for kidney failure. Patient mortality is extremely high, with cardiovascular disease (CVD) being the leading cause of death. This results from both a high underlying burden of cardiovascular disease, as well as additional physiological stress from the HD procedure itself. Clinical observations indicate that HD is associated with microvascular dysfunction (MD), underlining the need for a fundamental pathophysiological assessment of the microcirculatory consequences of HD. We therefore successfully developed an experimental small animal model, that allows for a simultaneous real-time assessment of the microvasculature. Using in-house built ultra-low surface area dialyzers and miniaturized extracorporeal circuit, we successfully dialyzed male Wistar Kyoto rats and combined this with a simultaneous intravital microscopic observation of the EDL microvasculature. Our results show that even in healthy animals, a euvolemic HD procedure can induce a significant systemic hemodynamic disturbance and induce disruption of microvascular perfusion (as evidence by a reduction in the proportion of the observed microcirculation receiving blood flow). This study, using a new small animal hemodialysis model, has allowed direct demonstration that microvascular blood flow in tissue in skeletal muscle is acutely reduced during HD, potentially in concert with other microvascular beds. It shows that preclinical small animal models can be used to further investigate HD-induced ischemic organ injury and allow rapid throughput of putative interventions directed at reducing HD-induced multi-organ ischemic injury.

Non-invasive Systemic Hemodynamic Index in Vascular Risk Stratification Tailored for Hypertensives

Vascular dysfunction is a key hallmark of hypertension and related cardiovascular outcomes. As a well-known hemodynamic disease, hypertension is characterized by abnormal ventricular-vascular interactions. Complementing non-invasive systemic hemodynamics in hypertensive vascular risk assessment is of promising significance. We aimed to investigate the effects of abnormal hemodynamic states other than elevated blood pressure on vascular damage and establish a united index of systemic hemodynamics for generalized vascular risk evaluation. Non-invasive systemic hemodynamics, assessed by impedance cardiography, was compared among blood pressure stages. Vascular function was evaluated by flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV). Systemic hemodynamics was obtained from a total of 88 enrollees with a mean (±SD) systolic blood pressure 140 (±17) mm Hg, and aged 17 to 91 years. Both stroke systemic vascular resistance index and left stroke work index exhibited a significant alteration among blood pressure stages (p &lt; 0.001; p = 0.01, respectively), whereas heterogeneous hemodynamic and vascular function subsets existed within similar blood pressure. In addition, blood pressure categories failed to recognize between-group differences in endothelial dysfunction (p = 0.88) and arterial stiffness (p = 0.26). An increase in myocardial contractility and a parallel decrease in afterload was associated with the decline of vascular dysfunction. Systemic Hemodynamic Index (SHI), as a surrogate marker, demonstrated a significantly negative correlation with vascular damage index (VDI, r = −0.49, p &lt; 0.001). These findings illustrate that systemic hemodynamics underlying hypertensives provides more vascular information. The SHI/VDI score may be a feasible tool for cardiovascular function assessment.

Cerebral and systemic hemodynamic effect of recurring seizures

The increase in neuronal activity induced by a single seizure is supported by a rise in the cerebral blood flow and tissue oxygenation, a mechanism called neurovascular coupling (NVC). Whether cerebral and systemic hemodynamics are able to match neuronal activity during recurring seizures is unclear, as data from rodent models are at odds with human studies. In order to clarify this issue, we used an invasive brain and systemic monitoring to study the effects of chemically induced non-convulsive seizures in sheep. Despite an increase in neuronal activity as seizures repeat (Spearman’s ρ coefficient 0.31, P < 0.001), ictal variations of cerebral blood flow remained stable while it progressively increased in the inter-ictal intervals (ρ = 0.06, P = 0.44 and ρ = 0.22; P = 0.008). We also observed a progressive reduction in the inter-ictal brain tissue oxygenation (ρ = − 0.18; P = 0.04), suggesting that NVC was unable to compensate for the metabolic demand of these closely repeating seizures. At the systemic level, there was a progressive reduction in blood pressure and a progressive rise in cardiac output (ρ = − 0.22; P = 0.01 and ρ = 0.22; P = 0.01, respectively), suggesting seizure-induced autonomic dysfunction.

Fractional spinal anesthesia and systemic hemodynamics in frail elderly hip fracture patients

Background: Aging and frailty make the elderly patients susceptible to hypotension following spinal anesthesia. The systemic hemodynamic effects of spinal anesthesia are not well known. In this study, we examine the systemic hemodynamic effects of fractional spinal anesthesia following intermittent microdosing of a local anesthetic and an opioid.Methods: We included 15 patients aged over 65 with considerable comorbidities, planned for emergency hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. Invasive mean arterial pressure (MAP), cardiac index, systemic vascular resistance index, heart rate and stroke volume index were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15µg were administered with 25 minutes in between. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHgResults: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.003-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes after the first dose. Cardiac index, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the first dose, none of the systemic haemodynamic variables were affected.Conclusion: Fractional spinal anesthesia causes a low incidence of hypotension, induced mainly by a systemic venodilation, causing a decrease in venous return and fall in cardiac output. Our results show that fractional spinal anesthesia is a safe technique from a hemodynamic point of view and is probably underutilized in high-risk, elderly hip fracture patients

Correlation between Perfusion Index and Left Ventricular Output in Healthy Late Preterm Infants

Aim The perfusion index (PI) is a noninvasive marker derived from photoelectric plethysmographic signals in pulse oximetry in the evaluation of peripheral perfusion. This study was aimed to determine the correlation between PI and left ventricular output (LVO) in healthy late preterm infants at 48th hour of life. Methods With new generation pulse oximeter (MASIMO Rad 7 Oximeter) pre- and post-ductal PI values were recorded from healthy late preterm babies at the 48th hour of life. PI was determined simultaneously with LVO as measured by transthoracic echocardiography. Results A total of 50 late preterm babies were included in the study. The mean gestational age of the cases was 35.4 ± 0.7 weeks and the birth weight was 2,586 ± 362 g. Mean pre- and post-ductal PI values at the postnatal 48th hour of babies' life were found to be 2.0 ± 0.9 and 1.7 ± 1.1. The mean LVO value was 438 ± 124, LVO/kg 175 ± 50. When the LVO value was normalized according to the babies' body weight, there was no statistically significant correlation between the pre- and post-ductal PI and the LVO/kg value (r <0.2, p >0.05 in both comparisons). Conclusion There was no correlation between pre- and post-ductal PI and LVO values in healthy late preterm infants. This may be due to the failure of the LVO, a systemic hemodynamic parameter, to accurately reflect microvascular blood flow due to incomplete maturation of the sympathetic nervous system involved in the regulation of peripheral tissue perfusion in preterm babies. Key Points

Kidney Microcirculation as a Target for Innovative Therapies in AKI

Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of function and damage. The renal microcirculation plays a crucial role in maintaining the kidney’s functional and structural integrity for oxygen and nutrient supply and waste product removal. However, alterations in microcirculation and oxygenation due to renal perfusion defects, hypoxia, renal tubular, and endothelial damage can result in AKI and the loss of renal function regardless of systemic hemodynamic changes. The unique structural organization of the renal microvasculature and the presence of autoregulation make it difficult to understand the mechanisms and the occurrence of AKI following disorders such as septic, hemorrhagic, or cardiogenic shock; ischemia/reperfusion; chronic heart failure; cardiorenal syndrome; and hemodilution. In this review, we describe the organization of microcirculation, autoregulation, and pathophysiological alterations leading to AKI. We then suggest innovative therapies focused on the protection of the renal microcirculation and oxygenation to prevent AKI.