Vasoconstriction in isolated goat aorta does not increase mean aortic pressure

Vasoconstriction in small arteries and arterioles is known to increase resistance to flow, while vasoconstriction in large arteries and aorta is known to decrease their compliance. Besides this general understanding, there is no systematic documentation on what happens to small artery compliance and large artery resistance during vasoconstriction and the corresponding alterations in vascular pressure. The aim of the study is to assess the effect of adrenaline on goat aortae and small arteries in terms of resistance and compliance.Isolated goat aortae and small arteries were perfused with a pulsatile pump and lumen pressure was recorded before and after addition of adrenaline. In the aortae, systolic pressure increased, diastolic pressure decreased, pulse pressure increased (p = 0.018, WSR); but the mean pressure remained the same (p = 0.357, WSR). Small artery vasoconstriction caused an increase in systolic, diastolic and mean pressures (p = 0.028, WSR). Using length, radius, and thickness data from the tissues and the tubes of the experimental set-up, electrical models were simulated to understand the biological data. The simulations allow us to infer that vasoconstriction in aorta leads to a reduction in compliance, but an increase in resistance if any, is not sufficient to change the mean aortic pressure. On the other hand, vasoconstriction in small arteries increases resistance, but a decrease in compliance if any, does not affect any of the four pressure parameters measured. Vasoconstriction in aorta decreases compliance and therefore increases pulse pressure but does not change resistance significantly enough to alter mean pressure.Key Points SummaryThe main aim of the study is to understand where exactly resistance (R) and compliance (C) components of the vasculature occur. There is no definitive evidence for the effect of large artery vasoconstriction on resistance and hence the mean arterial pressure.The manuscript presents biological experiments studying the pressure response of goat aorta and small arteries to adrenaline (invitro) and the interpretations using equivalent electrical models.The study shows that in aorta and large arteries, vasoconstriction does not lead to a reduction in lumen diameter sufficient to cause a rise in resistance and mean pressure as compared to small arteries.Knowledge of exact location of R and C in the arterial tree enables re-assessment of the differential action of vasoactive drugs on resistance versus compliance vessels once we resolve beat-to-beat R and C changes in response to a drug. This way antihypertensive therapy can be tailored to address the specific cause of the type of hypertension.

Intravenous Calcium as a Pressor in a Swine Model of Hypoxic Lifeless Shock

Background: Resuscitation from hypoxic lifeless shock (LS, previously called pseudo-PEA) is often associated with hypotension refractory to catecholamine pressors. We hypothesized that this post-resuscitation state may be associated with hypocalcemia and the hypotension responsive to intravenous calcium. Results: Using pre-existing data from our hypoxic swine LS model, we measured blood pressure, hemodynamics, and electrolytes. In 9 animals with refractory hypotension we administered 37 boluses of intravenous calcium in the dosage range of 5 -20 mg. Physiological data were analyzed on a heartbeat by heartbeat basis. The midpoint of the calcium response was defined using change of curvature feature detection. Hemodynamic parameters were shifted such that the value at the midpoint was equal to zero. Comparisons were made between the average values in the time period 40-35 seconds before the bolus and 35-40 seconds after the bolus. Of the 37 administered boluses, 34 manifested a reaction in the blood pressure, with mean aortic pressure, systolic and diastolic pressures all increasing post bolus administration. Conclusions: Ionized hypocalcemia and hypotension may be common after resuscitation from hypoxic lifeless shock. Administration of intravenous calcium may be associated with a pressor-like response. Hypocalcemia is an etiology for hypotension, and intravenous calcium as a therapy in this setting should be further investigated.

P18 The utility and validity of intracoronary administration of nicorandil alone for the measurement of fractional flow reserve in patients with intermediate coronary stenosis

Backgrand Recently, intracoronary nicorandil (ICN) administration in addition to intravenous adenosine 5"-triphosphate (IVATP) is generally used to achieve maximal hyperemia for evaluating fractional flow reserve (FFR). This study investigated the usefulness and safety of ICN alone compared with IVATP and ICN during IVATP for the achievement of maximal hyperemia in patients with suspected angina pectoris. Methods Two-hundred-ten angiographically intermediate lesions in two-hundred-seven patients who underwent FFR assessments were enrolled. FFR was measured after ICN (2mg/5seconds), IVATP (150µg/kg/min) for 2 minutes, IVATP (210µg/km/min) for 2 minutes, and ICN (2mg/5seconds) during IVATP (150µg/kg/min). Maximal hyperemia was defined as the lowest FFR measured among each method. Results During the protocol, 92% of patients achieved maximal hyperemia with ICN2mg, 54% with IVATP 150µg/kg/min, 91% with IVATP 210µg/kg/min, and 99% with ICN2mg during IVATP 150µg/kg/min, respectively. The FFR obtained with ICN2mg were strongly correlated with those obtained with ICN2mg during IVATP150µg/kg/min (r²=0.93, P< 0.001). The mean aortic pressure drop during hyperemia was significantly lower in ICN2mg than in IVATP 150µg/kg/min, IVATP 210µg/kg/min, and ICN2mg during IVATP 150µg/kg/min(9 ± 10, 11 ± 14, 24 ± 17, and 27 ± 19mmHg, p < 0.001, respectively). Despite no side effects reported during hyperemia with ICN2mg alone, transient atrioventricular block was observed in 1(1%) patient with IVATP 150µg/kg/min and 9(4%) patients with IVATP 210µg/kg/min. Also, 20 (10%) patients with IVATP 150µg/kg/min and 56(27%) with IVATP210µg/kg/min experienced chest discomfort during hyperemia. Conclusions The intracoronary administration of NIC2mg is safe and well tolerated, and shortens the procedure. Furthermore, intracoronary NIC2mg produced a more pronounced hyperemia than IVATP and may be the preferred mode of application for the assessment of FFR.

Abstract 100: Intravenous Calcium as a Pressor After Hypoxic Cardiac Arrest

Background: Resuscitation from hypoxic cardiac arrest presenting with pseudo-electromechanical dissociation (P-EMD) may be associated with hypotension after ROSC. This hypotension may be refractory to catecholamine pressors. Reversing hypotension is critical for stabilizing patients successfully resuscitated from P-EMD, so other therapeutic avenues should be explored. Hypothesis: The post-resuscitation phase after hypoxic pseudo-EMD cardiac arrest may be associated with hypocalcemia. The refractory hypotension may be responsive to intravenous calcium. Methods: Using our hypoxic pseudo-EMD swine model, we measured blood pressure, hemodynamics, and electrolytes after ROSC. In 12 animals with refractory hypotension we administered 37 boluses of intravenous calcium in the dosage range of 5 -20 mg. Physiological data were analyzed on a heartbeat by heartbeat basis. The midpoint of the calcium response was defined using change of curvature feature detection. Hemodynamic parameters were shifted such that the value at the midpoint was equal to zero. Comparisons were made between the average values in the time period 40-35 seconds before the bolus and 35-40 seconds after the bolus. Results: Of the 37 administered boluses, 34 manifested a reaction in the aortic blood pressure. Mean aortic pressure, systolic and diastolic pressures all increased due to the calcium bolus. Aggregating the timepoints in the range -40 s to -36 s and comparing with the timepoints in the range 36 s to 40 s shows that the mean aortic pressure increased 11.2 ± 0.6 mmHg, the systolic pressure increased 16.2 ± 0.8 mmHg, and the diastolic pressure increased 8.0 ± 0.5 mmHg. Conclusions: Resuscitation from hypoxic pseudo-EMD is often associated with hypotension and hypocalcemia. Administration of intravenous calcium is associated with an abrupt pressor-like response. Calcium as a therapeutic in this setting should be further studied.

PASSIVE COUNTERPULSATION: BIOMECHANICAL RATIONALE AND CLINICAL VALIDATION

Intra-aortic balloon counterpulsation (IABP) is the leading technique for cardiovascular support in most critical conditions. The beneficial effects of the procedure are widely known, but some drawbacks remain unsolved: high cost and controversial effect in presence of cardiac arrhythmia, both related to the control of intra-aortic balloon inflation and deflation. This paper describes the clinical validation of a completely passive solution (PIABP), which substitutes the time-controlled pumping system by a simple pressure-controlled reservoir. The test was performed on 10 patients, switching from IABP to PIABP and changing the reservoir pressure to obtain an optimal effect in terms of mean aortic pressure increase as an estimate of cardiac output. For each patient the reservoir pressure was increased in 10 mmHg steps and the aortic pressure was recorded together with electrocardiogram. The PIABP showed a positive effect in all the patients, with a significant increase of the mean aortic pressure (+6.5%, p < 0.05) and of the mean pressure of the aortic pulse diastolic phase (+7%, p < 0.05). The change of heart rate between basal and optimal effect condition was not significant. Also an unexpected, significant increase of aortic maximal pressure (8%, p < 0.05) was found. The proposed passive solution cannot be a substitute of the active one in all the situation, but may be useful in border line conditions, where the IABP is no more necessary but a ventricular support is still desirable.

Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation

Low-amplitude pulses to the vasculature increase pulsatile shear stress to the endothelium. This activates endothelial nitric oxide (NO) synthase (eNOS) to promote NO release and endothelial-dependent vasodilatation. Descent of the dicrotic notch on the arterial pulse waveform and a-to- b ratio ( a/ b; where a is the height of the pulse amplitude and b is the height of the dicrotic notch above the end-diastolic level) reflects vasodilator (increased a/ b) and vasoconstrictor effects (decreased a/ b) due to NO level change. Periodic acceleration (pGz) (motion of the supine body head to foot on a platform) provides systemic additional pulsatile shear stress. The purpose of this study was to determine whether or not pGzapplied to rats produced endothelial-dependent vasodilatation and increased NO production, and whether the latter was regulated by the Akt/phosphatidylinositol 3-kinase (PI3K) pathway. Male rats were anesthetized and instrumented, and pGzwas applied. Sodium nitroprusside, NG-nitro-l-arginine methyl ester (l-NAME), and wortmannin (WM; to block Akt/PI3K pathway) were administered to compare changes in a/ b and mean aortic pressure. Descent of the dicrotic notch occurred within 2 s of initiating pGz. Dose-dependent increase of a/ b and decrease of mean aortic pressure took place with SNP. l-NAME produced a dose-dependent rise in mean aortic pressure and decrease of a/ b, which was blunted with pGz. In the presence of WM, pGzdid not decrease aortic pressure or increase a/ b. WM also abolished the pGzblunting effect on blood pressure and a/ b of l-NAME-treated animals. eNOS expression was increased in aortic tissue after pGz. This study indicates that addition of low-amplitude pulses to circulation through pGzproduces endothelial-dependent vasodilatation due to increased NO in rats, which is mediated via activation of eNOS, in part, by the Akt/PI3K pathway.