Variations In Systemic Arterial Pressure Research Articles

(093) The Light-Controlled Nitric Oxide Donor “NORD-1” may Improve Erectile Function Without Hypotension and Tissue Damage in Rats With Neurogenic Erectile Dysfunction

Abstract Introduction Radical prostatectomy (RP) often causes erectile dysfunction (ED) because of cavernous nerve damage during surgery. This damage results in a decrease of nitric oxide (NO) in the penile corpus cavernosum. Therefore, NO supplementation is considered to be effective for post RP ED. However, NO has systemic side effects such as headache and hypotension. Recently, a red-light-controlled NO donor “NORD-1”, developed by our group, enables spatially and temporally controlled NO release by light irradiation. Our previous study reported that NORD-1 combined with red-light irradiation is effective for neurogenic ED model rats with bilateral cavernous nerve injury (BCNI). However, the side effects of the treatment have not yet been discussed. Objective The study aimed to investigate the potency of side effects associated with the combination of NORD-1 and red-light irradiation, using a ED rat model with BCNI. Methods In this study, eight-week-old male Wistar-ST rats were used. The rats were divided into four groups: Sham+SiR650 (control compound), Sham+NORD-1, BCNI+SiR650, and BCNI+NORD-1 (n=6). The sham or BCNI surgery was performed under anesthesia in each group. BCNI surgery was performed by crushing the cavernous nerves bilaterally. Four weeks post-surgery, erectile function before and after the injection of each reagent into the penile corpus cavernosum was evaluated based on the changes in intracavernous pressure (ICP) under electrostimulation of the cavernous nerve. After the administration of each reagent, the changes in ICP with and without light irradiation were also evaluated. ICP during electrostimulation was totally measured three times; once without reagent and light, once with reagent and without light and once with reagent and light. The variations in systemic arterial pressure during electrostimulation were also analyzed. After the experiment, penile samples were collected to observe NORD-1 localization using a fluorescence microscope. In addition, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate apoptosis in the corpus cavernousm. Results Before administering each reagent without light irradiation, the ICP/mean arterial pressure (MAP) ratios under stimulation in the BCNI+SiR650 and BCNI+NORD-1 groups were significantly lower than those in the Sham+SiR650 (P < 0.01) and Sham+NORD-1 (P < 0.05) groups. After administering each reagent without light irradiation, the ICP/MAP ratios in the BCNI+SiR650 and BCNI+NORD-1 groups remained significantly lower than those in the Sham+SiR650 and Sham+NORD-1 group (P < 0.05 and P < 0.01, respectively). After administering each reagent with light irradiation, the ICP/MAP ratios in the Sham+NORD-1 and BCNI+NORD-1 groups were significantly higher than those in the Sham+SiR650 (P < 0.01) and BCNI+NORD-1 (P < 0.01) groups, respectively. The changes of MAP during electrostimulation were not different under three different conditions in all four groups. Fluorescence of NORD-1 was detected only in corpus cavernousum which means it was not detected in urethra and dorsal vein of penis. Apoptosis was not detected in corpus cavernousum in all four groups. Conclusions The combination of NORD-1 and light irradiation is effective for neurogenic ED in rats with cavernous nerve injury. The treatment may not cause hypotension and tissue damage. Disclosure No

Further cautions for the use of ventilatory-induced changes in arterial pressures to predict volume responsiveness

Variations in systemic arterial pressure with positive-pressure breathing are frequently used to guide fluid management in hemodynamically unstable patients. However, because of the complex physiology that determines the response, there are important limitations to their use. Two papers in a previous volume add pulmonary hypertension as limitations. Uncritical use of ventilatory-induced changes in arterial pressure can lead to excessive volume therapy and potential clinical harm, and they must be used with respect and thought.

Initial Acute In Vivo Performance of the Cleveland Clinic PediPump Left Ventricular Assist Device

The PediPump is a small ventricular assist device (VAD) with a hydraulic output range designed to support children from newborns to adolescents. The present report describes our initial evaluation of the PediPump as a left VAD in an acute sheep model. The PediPump was implanted in two sheep (50.8 and 62.7 kg). Pump speed was adjusted to achieve a flow of 2 L/min with the naturally occurring preload and afterload conditions to evaluate pump performance under a steady hemodynamic state for 4 hours. Upon completion, pump performance was evaluated under various blood pressure and heart rate conditions. During steady-state evaluations, the ascending aortic flow and pump speed varied slightly depending on systemic arterial pressure variations. During the hemodynamic manipulation studies, flows ranged between 0.5 and 3.2 L/min with pump speeds of 5,200-16,200 rpm and motor current of 0.06-0.75 A. The PediPump demonstrated good initial hemodynamic performance for use as an implantable left VAD. However, some depositions were detected at the time of explanation, mainly at the rear of the pump. We are continuing with further acute studies to evaluate pump performance in anticipation of beginning chronic studies to evaluate long-term biocompatibility.

In Vitro Evaluation of Variability in Systemic Arterial Pressure Changes During Closed vs Open-bridge Extracorporeal Life Support 234

Introduction: Extracorporeal life support (ECLS) is used for the support of cardiorespiratory failure. The standard ECLS circuit has a bridge between venous drainage and infusion tubing. This allows temporary dissociation of the patient from the ECLS circuit. The bridge is opened intermittently to prevent clotting (called flashing). Changes in systemic arterial pressure (SAP) due to changes in systemic vascular resistance (SVR) have been reported during flashing of the bridge which can be avoided if the bridge is kept partially open. An in vitro method is developed to study variations in SAP during closed and open-bridge ECLS.

Mathematical considerations for modeling cerebral blood flow autoregulation to systemic arterial pressure.

The shape of the autoregulation curve for cerebral blood flow (CBF) vs. pressure is depicted in a variety of ways to fit experimentally derived data. However, there is no general empirical description to reproduce CBF changes resulting from systemic arterial pressure variations that is consistent with the reported data. We analyzed previously reported experimental data used to construct autoregulation curves. To improve on existing portrayals of the fitting of the observed data, a compartmental model was developed for synthesis of the autoregulation curve. The resistive arterial and arteriolar network was simplified as an autoregulation device (ARD), which consists of four compartments in series controlling CBF. Each compartment consists of a group of identical vessels in parallel. The response of each vessel category to changes in perfusion pressure was simulated using reported experimental data. The CBF-pressure curve was calculated from the resistance of the ARD. The predicted autoregulation curve was consistent with reported experimental data. The lower and upper limits of autoregulation (LLA and ULA) were predicted as 69 and 153 mmHg, respectively. The average value of the slope of the CBF-pressure curve below LLA and beyond ULA was predicted as 1.3 and 3.3% change in CBF per mmHg, respectively. Our four-compartment ARD model, which simulated small arteries and arterioles, predicted an autoregulation function similar to experimental data with respect to the LLA, ULA, and average slopes of the autoregulation curve below LLA and above ULA.

Buffering of respiratory variations in venous return by right ventricle: a theoretical analysis

The role of the right ventricle (RV) in buffering systemic venous return, thereby dampening respiratory-induced variations, left ventricular (LV) stroke volume, and systemic arterial pressure variations was examined using a computer model of the cardiovascular system. Respiration was simulated by cyclical variations in intrathoracic and abdominal pressures (cycle time 5 heartbeats), causing a 43-ml fluctuation in venous return per heartbeat (mean 71 ml) compared with fluctuations of 19 ml in RV stroke volume, 6 ml in pulmonary venous flow, and only 3 ml in LV stroke volume. On a percentage basis, the RV provided 56% of the total buffering of systemic venous return, the lungs another 30%, whereas the LV only 7%. A 10-fold increase in RV diastolic compliance increased the RV stroke volume variations from 26 to 57% of the venous return variations; a 10-fold increase in RV elastance increased them from 24 to 60%, whereas decreasing pulmonary arterial pressure from 28 to 10 mmHg increased them from 28 to 56%. The results also suggest that an underrecognized function of the RV is to buffer systemic venous return and thereby keep LV stroke volume relatively constant.

Venous collapse and the respiratory variability in systemic venous return.

Venous collapse limits systemic venous return, but its effects on beat to beat respiratory venous return variations are less well known. The aim of this study was to investigate the effects of venous collapse on respiratory variations in venous return. A model of venous collapse which included both an increase in haemodynamic resistance to flow and an increase in vessel compliance was incorporated in a previously described cardiovascular model. Respiration was simulated by 5 mm Hg swings of intrathoracic pressure (PTH) at different mean pressures such that the abdominal vena cava and jugular vein were either fully collapsed (mean PTH -11 mm Hg), in the transition zone between collapse and distension (mean PTH -6 mm Hg), or fully distended (mean PTH 9 mm Hg). The mean and standard deviations over each respiratory cycle of the venous return volume (flow integral over heart cycle) and the abdominal vena caval volume were recorded. Different venous return volume variabilities in the three operating zones of the vena cava were identified: (1) reduced variability in the collapsed zone associated with the increased haemodynamic resistance [venous return 93(SD 6) ml, abdominal vena caval volume 30(3) ml. absolute right atrial pressure -6.3(1.1) mm Hg]; (2) increased variability in the transition zone [venous return 86(24) ml, abdominal vena caval volume 81(15) ml, right atrial pressure -2.2(0.8) mm Hg]; (3) low variability in the distended zone [venous return 42(11) ml, abdominal vena caval volume 120(2) ml, right atrial pressure 10.1(1.1) mm Hg]. The greater the change in compliance with collapse the greater the increase in flow variability in the transition zone; with no change in compliance there was no increased flow variability in the transition zone. The results suggest that venous collapse increases the respiratory variations in venous return in the transition zone. As venous return variations contribute to arterial pressure variations, the collapsible nature of the great veins may influence respiratory variations in systemic arterial pressure.

Studies of experimental cervical spinal cord transection. Part IV: Effects of cervical spinal cord transection on myocardial blood flow in anesthetized dogs.

✓ Effects of cervical cord transection on total and regional myocardial blood flow and coronary vascular resistance were studied in anesthetized dogs using 15-µm microspheres. Left atrial catheters were inserted by thoracotomy in 10 dogs and iodine-125-labeled microspheres were injected to measure baseline tissue blood flows by means of the reference flow technique. Four dogs then underwent laminectomy of the C-6 vertebra (control group), and six underwent laminectomy and cord transection (experimental group). Microspheres labeled with cerium-141, strontium-85, and scandium-46 were injected at 15, 30, and 120 minutes, respectively, after surgical intervention. The dogs were sacrificed, and the radioisotope content of specimens of epicardial, mid-myocardial, and endocardial tissues was determined by differential spectrometry, and tissue blood flow was calculated in relation to arterial reference specimens. No significant differences in baseline endocardial, epicardial, or mid-myocardial blood flow were detected between the control and experimental groups. Tissue blood flows fell significantly in all regions (p < 0.05 or less) at 15, 30, and 120 minutes after transection. No major alteration of the endocardial/epicardial flow ratio occurred, and no electrocardiographic or pathological evidence of ischemia was seen. When corrected for variations in systemic arterial pressure, no differences in coronary vascular resistance between control and cord-transected dogs were observed. These findings suggest that the decreased coronary blood flow following cervical cord transection is secondary to decreased mean arterial pressure rather than to altered coronary vascular resistance. Pharmacological augmentation of perfusion pressure may therefore be necessary to maintain adequate coronary blood flow in patients with acute cord injury who have pre-existent cardiac disease.

Respiratory Sinus Arrhythmia in Man: Relation to Cardiovascular Pressures

The relationship of respiratory sinus arrhythmia (RSA) to the accompanying oscillations of cardiovascular pressure has been studied in five healthy subjects. Tidal volume (VT) of 1.0, 1.5, and 2.0 1 at the breathing rate of 6 c-min-1 were used as reference. With identical VT oesophageal pressure was varied by negative inspiratory pressure (NIP) and intermittent positive-pressure ventilation (IPPV). Compared with control, NIP with 1.01 significantly increased RSA, the oscillations of brachial artery pressures (PBA), and the net filling pressures of the ventricles. IPPV did not significantly change the variations of PBA but reduced RSA and the respiratory variations of the right ventricular end-diastolic net pressure. During control breathing and with NIP the acceleration of heart rate during inspiration was associated with rising PBA and rising net filling pressures of both ventricles. The results indicate that RSA may be elicited by cardiovascular reflexes due to changes in venous filling of the heart rather than by the variations in systemic arterial pressure.

Respiratory Sinus Arrhythmia in Man: Relation to Cardiovascular Pressures

The relationship of repiratory sinus arrhythmia (RSA) to the accompanying oscillations of cardiovascular pressures has been studied in five healthy subjects. Tidal volumes (VT) of 1.0, 1.5, and 2.0 1 at a breathing rate of 6 c-min(-1) were used as reference. With identical VT, oesophageal pressure was varied by negative inspiratory pressure (NIP) and intermittent positive-pressure ventilation (IPPV). Compared with control, NIP with 1.01 significantly increased RSA, the oscillations of brachial artery pressures (PBA), and the net filling pressures of the ventricles. IPPV did not significantly change the variations of PBA but reduced RSA and the repiratory variations of the right ventricular end-diastolic net pressure. During control breathing and with NIP the acceleration of heart rate during inspiration was associated with rising PBA and rising net filling pressures of both ventricles. The results indicate that RSA may be elicited by cardiovascular reflexes due to changes in venous filling of the heart rather than by the variations in systemic arterial pressure.