Impaired balance between coronary blood flow and myocardial metabolism in postpartum swine.

Understanding of the mechanisms contributing to the increased maternal susceptibility for major adverse cardiovascular events in the postpartum period remains poor. Accordingly, this study tested the hypothesis that the balance between coronary blood flow and myocardial metabolism is compromised during the puerperium period (35-45 days post-delivery) in swine. Systemic and coronary hemodynamic responses were assessed in anesthetized, open-chest control (nonpregnant) and puerperium/postpartum swine at baseline and in response to intravenous infusion of dobutamine (1-30 µg/kg/min). Blood pressure and heart rate were lower in postpartum swine at baseline and in response to dobutamine (P < 0.05). Coronary blood flow and myocardial oxygen delivery were significantly diminished at baseline in postpartum swine (P < 0.001), which corresponded with ∼35% reduction in myocardial oxygen consumption (MVO2) (P < 0.001). Postpartum swine displayed enhanced retrograde coronary flow, larger cardiomyocyte area (P < 0.01) and marked capillary rarefaction (P < 0.01). The relationship between coronary blood flow and heart rate (P < 0.05) or MVO2 (P < 0.001) was significantly diminished in postpartum swine as dobutamine increased MVO2 up to ∼135% in both groups. This reduction in myocardial perfusion was associated with decreases in myocardial lactate uptake (P < 0.001), increases in coronary venous PCO2 (P < 0.01) and decreased coronary venous pH (P < 0.01). These findings suggest an impaired balance between coronary blood flow and myocardial metabolism could contribute to the increased incidence of maternal myocardial ischemia and premature death in the postpartum period.

Unraveling the Gordian knot of coronary pressure-flow autoregulation.

The coronary circulation has the inherent ability to maintain myocardial perfusion constant over a wide range of perfusion pressures. The phenomenon of pressure-flow autoregulation is crucial in response to flow-limiting atherosclerotic lesions which diminish coronary driving pressure and increase risk of myocardial ischemia and infarction. Despite well over half a century of devoted research, understanding of the mechanisms responsible for autoregulation remains one of the most fundamental and contested questions in the field today. The purpose of this review is to highlight current knowledge regarding the complex interrelationship between the pathways and mechanisms proposed to dictate the degree of coronary pressure-flow autoregulation. Our group recently likened the intertwined nature of the essential determinants of coronary flow control to the symbolically unsolvable "Gordian knot". To further efforts to unravel the autoregulatory "knot", we consider recent challenges to the local metabolic and myogenic hypotheses and the complicated dynamic structural and functional heterogeneity unique to the heart and coronary circulation. Additional consideration is given to interrogation of putative mediators, role of K+ and Ca2+ channels, and recent insights from computational modeling studies. Improved understanding of how specific vasoactive mediators, pathways, and underlying disease states influence coronary pressure-flow relations stands to significantly reduce morbidity and mortality for what remains the leading cause of death worldwide.

Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure.

The coronary circulation has an innate ability to maintain constant blood flow over a wide range of perfusion pressures. However, the mechanisms responsible for coronary autoregulation remain a fundamental and highly contested question. This study interrogated the local metabolic hypothesis of autoregulation by testing the hypothesis that hypoxemia-induced exaggeration of the metabolic error signal improves the autoregulatory response. Experiments were performed on open-chest anesthetized swine during stepwise changes in coronary perfusion pressure (CPP) from 140 to 40 mmHg under normoxic (n = 15) and hypoxemic (n = 8) conditions, in the absence and presence of dobutamine-induced increases in myocardial oxygen consumption (MVO2) (n = 5-7). Hypoxemia (PaO2 < 40 mmHg) decreased coronary venous PO2 (CvPO2) ~ 30% (P < 0.001) and increased coronary blood flow ~ 100% (P < 0.001), sufficient to maintain myocardial oxygen delivery (P = 0.14) over a wide range of CPPs. Autoregulatory responsiveness during hypoxemia-induced reductions in CvPO2 were associated with increases of autoregulatory gain (Gc; P = 0.033) but not slope (P = 0.585) over a CPP range of 120 to 60 mmHg. Preservation of autoregulatory Gc (P = 0.069) and slope (P = 0.264) was observed during dobutamine administration ± hypoxemia. Reductions in coronary resistance in response to decreases in CPP predominantly occurred below CvPO2 values of ~ 25 mmHg, irrespective of underlying vasomotor reserve. These findings support the presence of an autoregulatory threshold under which oxygen-sensing pathway(s) act to preserve sufficient myocardial oxygen delivery as CPP is reduced during increases in MVO2 and/or reductions in arterial oxygen content.

Prevalence of pharmacological and non-pharmacological coping mechanisms for anxiety management during the COVID-19 pandemic: investigating the transition to online learning among medical students.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a devastating effect on college students worldwide. Here, the authors aimed to determine the prevalence of anxiety and its related coping strategies, provide a theoretical basis for understanding self-prescription, and identify the factors contributing to stress and anxiety in medical students during the pandemic. METHODS: The authors conducted a cross-sectional study among medical students in Saudi Arabia from September to November 2020. They assessed anxiety using the GAD-7 scale based on seven core symptoms. The authors also examined perceived psychological stress using a single-item measure of stress, the factors contributing to stress during the transition to online learning and examinations, and related coping strategies. The Statistical Package for Social Sciences (SPSS) version 26.0 was used to examine the data for both descriptive and inferential analyses. Chi-square test, one-way ANOVA, and univariate linear regression were used to test the research hypotheses. RESULTS: The authors collected and analyzed data from 7116 medical students distributed across 38 medical colleges. Among them, 40% reported moderate to severe anxiety symptoms. Pre-clinical and female students experienced more stress than clinical and male students. 12.19% (n = 868) of respondents reported using medication during their college years. Among those, 58.9% (n = 512) had moderate to severe anxiety, and the most commonly used drug was propranolol (45.4%, n = 394). Among the studied sample, 40.4% (n = 351) decreased their medication use after switching to online teaching. Most students used these medications during the final exam (35.8%, n = 311) and before the oral exam (35.5%, n = 308). In terms of coping strategies, males were much more likely to use substances than females, who mainly resorted to other strategies. CONCLUSIONS: This study provides a national overview of the impact of COVID-19 on the mental health of medical students. The results indicated that the pandemic is associated with highly significant levels of anxiety. These findings can provide theoretical evidence for the need for supportive psychological assistance from academic leaders in this regard.

Chronic high-rate pacing induces heart failure with preserved ejection fraction-like phenotype in Ossabaw swine.

The lack of pre-clinical large animal models of heart failure with preserved ejection fraction (HFpEF) remains a growing, yet unmet obstacle to improving understanding of this complex condition. We examined whether chronic cardiometabolic stress in Ossabaw swine, which possess a genetic propensity for obesity and cardiovascular complications, produces an HFpEF-like phenotype. Swine were fed standard chow (lean; n = 13) or an excess calorie, high-fat, high-fructose diet (obese; n = 16) for ~ 18 weeks with lean (n = 5) and obese (n = 8) swine subjected to right ventricular pacing (180 beats/min for ~ 4 weeks) to induce heart failure (HF). Baseline blood pressure, heart rate, LV end-diastolic volume, and ejection fraction were similar between groups. High-rate pacing increased LV end-diastolic pressure from ~ 11 ± 1 mmHg in lean and obese swine to ~ 26 ± 2 mmHg in lean HF and obese HF swine. Regression analyses revealed an upward shift in LV diastolic pressure vs. diastolic volume in paced swine that was associated with an ~ twofold increase in myocardial fibrosis and an ~ 50% reduction in myocardial capillary density. Hemodynamic responses to graded hemorrhage revealed an ~ 40% decrease in the chronotropic response to reductions in blood pressure in lean HF and obese HF swine without appreciable changes in myocardial oxygen delivery or transmural perfusion. These findings support that high-rate ventricular pacing of lean and obese Ossabaw swine initiates underlying cardiac remodeling accompanied by elevated LV filling pressures with normal ejection fraction. This distinct pre-clinical tool provides a unique platform for further mechanistic and therapeutic studies of this highly complex syndrome.

Effects of Water Column Variations on Sound Propagation and Underwater Acoustic Communications.

Underwater sound propagation is very sensitive to geometric and environmental variations. The geometric variations are the motion of the source and/or receiver, while the environmental variations are due to surface motion and water column variations. In order to reduce the effects of these variations, it is necessary to understand their effects on sound propagation. In this paper, some water column variations are reported, and their effect on the underwater sound propagation is studied. These water column variations were observed during an experiment in the TrondheimFjord on 22 September 2016. Strong amplitude variations were observed in the channel impulse response during the experiment. The Doppler analysis was performed on the channel impulse response, which showed strong Doppler variations. The amplitude and Doppler variations suggested the presence of water column variations. To demonstrate the performance of the communication system, the time reversal combiner was implemented. The system performance was demonstrated by computing the mean squared error between the transmitted signal and the output of the combiner. The performance of the combiner degraded by ~2.5 dB in the presence of water column variations. Due to these variations, the amplitudes of the arrivals changed rapidly, which posed a great challenge for the time reversal combiner. These amplitude variations affected the focusing of the combiner and hence induced intersymbol interference and performance degradation. This work provides an insight into the effects of water column variations on underwater sound propagation and underwater acoustic communications.

How do Saudi diabetic patients perceive their illness? A multicenter survey using revised-illness perception questionnaire.

BACKGROUND: Illness perception questionnaires for various medical conditions have become more useful in recent years. However, very few have used this to address the issue of type 2 diabetes in Saudi Arabia. MATERIALS AND METHODS: This study was conducted among type 2 diabetic patients attending primary healthcare centers and Al Kharj Military Industries Corporation Hospital in Al Kharj, Saudi Arabia, during November 24, 2016, to April 24, 2017. SPSS used for analysis that included descriptive statistics, t-test, and a one-way analysis of variance (ANOVA). RESULTS: A total of 500 questionnaires were distributed, and 383 of them were returned; response rate about 77%. Majority of participants (80.4%) were educated, 69.5% were married, and 51% were females. About 57% were on OHA, and 57% had no other chronic disease. Most participants perceived that diabetes was hereditary (75%), and 62.4% thought it is due to diet or eating habits. About 80% participants believed that there is a lot they can do to control symptoms. About 73% participants believed they have the power to influence diabetes, whereas 78% think there is very little that can be done to improve diabetes and treatment can control diabetes. The Cronbach's alpha value for identity, timeline (cyclical), and emotional factors were relatively high, showing that these scales had a strong level of internal consistency. CONCLUSION: Saudis with type 2 diabetes mellitus had adequate knowledge of their disease. They agreed that diabetes was likely to be permanent and would have major consequences on their lives.

Molecular characterization of Acinetobacter baumannii isolated from Iraqi hospital environment.

Healthcare-associated items are a common source of acquired infections, and hospital-acquired infections cause significant mortality and morbidity worldwide. Acinetobacter baumannii is the most prevalent infection-causing organism in the hospital environment. Hospital articles and objects are the main sources of infection with the ability to transmit some of the pathogenic microorganisms such as A. baumannii, which is considered a serious problem in therapeutic treatments. In the current study, we isolated A. baumannii from hospital sources and evaluated its antibiotic resistance, virulence factors and resistance gene determinants. The isolates were identified phenotypically as well as genotypically using PCR. In addition, their capability for biofilm formation and ten other virulence factors were measured. Of 112 samples, 21 showed growth of the target organism. Apart from A. baumannii, isolates of Candida albicans, Staphylococcus sp., Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae were also grown. Antibiotic susceptibility test results considered all the A. baumannii to be multidrug-resistant isolates with the highest resistance being 100% to gentamycin, ciprofloxacin; the most effective antibiotics with 100% susceptibility was colistin and tigecycline. All A. baumannii isolates had MIC for ceftriaxone >32 mg/L. All A. baumannii isolates from the hospital environment showed multidrug resistance and had many virulence factors. They have long-term resistance to dry conditions and cause a serious public health issue.

Path specific Doppler compensation in time-reversal communications.

Passive time reversal (pTR) is a low complexity receiver scheme that uses multichannel probing for time signal refocusing, thus reducing time spreading and improving inter-symbol interference. Recognizing that signals traveling through different paths are subject to arrival-angle-related Doppler displacements, this letter proposes a further improvement to pTR that applies correcting frequency shifts optimized for beams formed along each specific path arrival angle. The proposed channel equalizer is tested with real data, and the results show that the proposed approach outperforms both pTR and the modified pTR channel combiners providing an MSE gain of 4.9 and 4.2 dB, respectively.

Role of norepinephrine & angiotensin II in the neural control of renal sodium & water handling in spontaneously hypertensive rats.

BACKGROUND & OBJECTIVES: A wealth of information concerning the essential role of renal sympathetic nerve activity (RSNA) in the regulation of renal function and mean arterial blood pressure homeostasis has been established. However, many important parameters with which RSNA interacts are yet to be explicitly characterized. Therefore, the present study aimed to investigate the impact of acute renal denervation (ARD) on sodium and water excretory responses to intravenous (iv) infusions of either norepinephrine (NE) or angiotensin II (Ang II) in anaesthetized spontaneously hypertensive rats (SHR). METHODS: Anaesthetized SHR were acutely denervated and a continuous iv infusion of NE (200 ng/min/ kg) or Ang II (50 ng/min/kg) was instigated for 1 h. Three 20-min urine clearances were subsequently collected to measure urine flow rate (UV) and absolute sodium excretion (U(Na)V). RESULTS: Higher UV and U(Na)V (P<0.05) were observed in denervated control SHR as compared to innervated counterparts. The administration of NE or Ang II to innervated SHR produced lower UV and U(Na)V (P<0.05 vs. innervated control SHR). Lower diuresis/natriuresis response to ARD was observed in NE-treated SHR compared to denervated control SHR (P<0.05). Salt and water excretions in denervated NE-treated SHR, however, were significantly higher (P<0.05) relative to the excretion levels in control denervated SHR. Conversely, there was a higher (all P<0.05) diuresis/natriuresis response to ARD when Ang II was administered to SHR compared to denervated control or innervated Ang II-treated SHR. INTERPRETATION & CONCLUSIONS: NE retains its characteristic antidiuretic/antinatriuretic action following ARD in SHR. Typical action of Ang II on salt and water excretions necessitates the presence of an intact renal innervation. Ang II is likely to facilitate the release of NE from renal sympathetic nerve terminals through a presynaptic site of action. Moreover, there is a lack of an immediate enhancement in the renal sensitivity to the actions of NE and Ang II following ARD in a rat model of essential hypertension.

Cardiovascular activity of the n-butanol fraction of the methanol extract of Loranthus ferrugineus Roxb

We investigated the vascular responses and the blood pressure reducing effects of different fractions obtained from the methanol extract of Loranthus ferrugineus Roxb. (F. Loranthaceae). By means of solvent-solvent extraction, L. ferrugineus methanol extract (LFME) was successively fractionated with chloroform, ethyl acetate and n-butanol. The ability of these LFME fractions to relax vascular smooth muscle against phenylephrine (PE)- and KCl-induced contractions in isolated rat aortic rings was determined. In another set of experiments, LFME fractions were tested for blood pressure lowering activity in anesthetized adult male Sprague-Dawley rats (250-300 g, 14-18 weeks). The n-butanol fraction of LFME (NBF-LFME) produced a significant concentration-dependent inhibition of PE- and KCl-induced aortic ring contractions compared to other fractions. Moreover, NBF-LFME had a significantly higher relaxant effect against PE- than against high K+-induced contractions. In anesthetized Sprague-Dawley rats, NBF-LFME significantly lowered blood pressure in a dose-dependent manner and with a relatively longer duration of action compared to the other fractions. HPLC, UV and IR spectra suggested the presence of terpenoid constituents in both LFME and NBF-LFME. Accordingly, we conclude that NBF-LFME is the most potent fraction producing a concentration-dependent relaxation in vascular smooth muscle in vitro and a dose-dependent blood pressure lowering activity in vivo. The cardiovascular effects of NBF-LFME are most likely attributable to its terpenoid content.

Cardiovascular activity of the n-butanol fraction of the methanol extract of Loranthus ferrugineus Roxb.

We investigated the vascular responses and the blood pressure reducing effects of different fractions obtained from the methanol extract of Loranthus ferrugineus Roxb. (F. Loranthaceae). By means of solvent-solvent extraction, L. ferrugineus methanol extract (LFME) was successively fractionated with chloroform, ethyl acetate and n-butanol. The ability of these LFME fractions to relax vascular smooth muscle against phenylephrine (PE)- and KCl-induced contractions in isolated rat aortic rings was determined. In another set of experiments, LFME fractions were tested for blood pressure lowering activity in anesthetized adult male Sprague-Dawley rats (250-300 g, 14-18 weeks). The n-butanol fraction of LFME (NBF-LFME) produced a significant concentration-dependent inhibition of PE- and KCl-induced aortic ring contractions compared to other fractions. Moreover, NBF-LFME had a significantly higher relaxant effect against PE- than against high K+-induced contractions. In anesthetized Sprague-Dawley rats, NBF-LFME significantly lowered blood pressure in a dose-dependent manner and with a relatively longer duration of action compared to the other fractions. HPLC, UV and IR spectra suggested the presence of terpenoid constituents in both LFME and NBF-LFME. Accordingly, we conclude that NBF-LFME is the most potent fraction producing a concentration-dependent relaxation in vascular smooth muscle in vitro and a dose-dependent blood pressure lowering activity in vivo. The cardiovascular effects of NBF-LFME are most likely attributable to its terpenoid content.

Interaction between renin-angiotensin and sympathetic nervous systems in a rat model of pressure overload cardiac hypertrophy.

1 A raised cardiac workload activates neurohormones which will increase muscle mass and shift contractility to the right along the Frank-Starling curve. 2 This study examined the interaction between the SNS and RAS in contributing to vascular responsiveness following the development of cardiac hypertrophy due to aortic banding. 3 Sprague Dawley rats (180-200 g) were assigned to one of six groups; Normal, Sham-operated, Aortic Banded (AB), Aortic Banded treated with losartan (ABLOS), Aortic Banded treated with 6-hydroxydopamine (ABSYMP) and Aortic banded treated with both losartan and 6-hydroxydopamine (ABSYMPLOS). A constricting band was placed around the supra renal aorta on day zero with drug treatment from day 37 to day 44. Vasopressor responses to noradrenaline, phenylephrine, methoxamine and angiotensin II were measured on day 45. 4 The magnitudes of the MAP responses to all vasoactive agents, expressed as percentage changes, were similar in Normal and Sham groups, but reduced in the AB group. ABLOS group showed attenuated response to ANGII whereas all responses were enhanced in the ABSYM group. 5 A positive interaction between the two systems was observed with alpha(1A)-adrenoceptors identified as a major component of SNS and AT(1) receptors of RAS to induce vasopressor effects.

Evaluation of the anti-pyretic potential of Orthosiphon stamineus Benth standardized extract.

The anti-pyretic activity of a standardized methanol/water (50/50) extract of Orthosiphon stamineus Benth. (SEOS) was investigated for its effect on normal body temperature and yeast-induced pyrexia in Sprague Dawley (SD) rats. The SEOS showed no effect on normal body temperature. Doses of 500 and 1000 mg/kg body weight of SEOS significantly reduced the yeast-induced elevation in body temperature. This effect persisted up to 4 h following the administration of the extract. The anti-pyretic effect of SEOS was comparable with that of paracetamol (acetaminophen in U.S) (150 mg/kg p.o.), a standard anti-pyretic agent. HPLC study revealed that rosmarinic acid, sinensetin, eupatorin and tetramethoxyflavone were present in SEOS in the amounts of 7.58%, 0.2%, 0.34% and 0.24% respectively. The LD(50) of the extract in rats was higher than 5000 mg/kg body weight. Therefore, the present study ascertained that SEOS possesses a significant anti-pyretic activity.

Effect of acute unilateral renal denervation on renal hemodynamics in spontaneously hypertensive rats.

1 This study was undertaken to characterize the renal responses to acute unilateral renal denervation in anaesthetized spontaneously hypertensive rats (SHR) by examining the effect of acute unilateral renal denervation on the renal hemodynamic responses to a set of vasoactive agents and renal nerve stimulation. 2 Twenty-four male SHR rats underwent acute unilateral renal denervation and the denervation was confirmed by significant drop (P < 0.05) in renal vasoconstrictor response to renal nerve stimulation along with marked diuresis and natriuresis following denervation. After 7 days treatment with losartan, the overnight fasted rats were anaesthetized (sodium pentobarbitone, 60 mg kg(-1) i.p.) and renal vasoconstrictor experiments were performed. The changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine, methoxamine and angiotensin II. 3 The data showed that there was significantly (all P < 0.05) increased renal vascular responsiveness to the vasoactive agents in denervated rats compared to those with intact renal nerves. In losartan-treated denervated SHR rats, there were significant (all P < 0.05) reductions in the renal vasoconstrictor responses to neural stimuli and vasoactive agents as compared with that of untreated denervated SHR rats. 4 The data obtained in denervated rats suggested an enhanced sensitivity of the alpha(1)-adrenoceptors to adrenergic agonists and possible increase of AT(1) receptors functionality in the renal vasculature of these rats. These data also suggested a possible interaction between sympathetic nervous system and renin-angiotensin system in terms of a crosstalk relationship between renal AT(1) and alpha(1)-adrenoceptor subtypes.

The clinical value of cathepsin-D and TNF-alpha in bladder cancer patients.

This study included 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 were operable cases and 31 non-operable). Serum tumor necrosis factor alpha (TNF-alpha) was determined using the enzyme immunoassay reagents supplied by Medgenix Diagnostics, Belgium. Cytosol Cathepsin-D was estimated using the immunoradiometric assay supplied by CIS BIO International, France. The results revealed that at 100% and 90% specificities, cytosol Cathepsin-D had 35.7% and 59.5% sensitivity in bladder cancer patients. Serum TNF-alpha showed sensitivity of 17.0% and 55.0% at 100% and 90% specificities in operable bladder cancer patients and 48.0% and 77.0% in non-operable cases respectively. Cytosol cathepsin D and TNF-alpha did not show prognostic values like positive correlation with tumor stages, grades or association of tumors with bilharzial ova or lymph node involvement.

Cathepsin-D and TNF-alpha in bladder cancer.

In a study of 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 of them are operable cases and 31 are non-operable ones), serum tumor necrosis factor alpha (TNF-alpha) and cytosolic Cathepsin-D were estimated. Though both potential markers were elevated in bladder cancer patients, neither Cathepsin-D nor TNF-alpha showed associations of prognostic value since there were no positive correlations with tumor stages, grades or association of tumors with bilharzial ova or lymph node involvement.