Increase In Mean Aortic Pressure Research Articles

Chronic maternal hypercortisolemia models stress-induced adverse birth outcome and altered cardiac function in newborn lambs.

Maternal stress in pregnancy is thought to be a contributing factor in adverse pregnancy outcomes, including stillbirth and prematurity. Previous studies in our laboratory have shown that chronic elevation in maternal cortisol concentration in ewes (by maternal infusion of 1 mg/kg/day) during the late gestation increased the incidence of stillbirth and altered fetal heart rate and blood pressure at birth. We designed the current study to test the effect of chronically elevated maternal cortisol on fetal cardiac adaption from in utero life to ex utero life. The combined risk of stillbirth or prematurity was significantly greater in the pregnancies with maternal hypercortisolemia; in this cohort, 40% of the lambs of cortisol-infused ewes died in utero or at birth compared with 25% of lambs of control ewes, and 24% of lambs of cortisol-infused ewes were born preterm, whereas no lamb was born preterm in the control group. Compared with control lambs, the lambs of cortisol-infused ewes born at full term exhibited a significant increase in mean aortic pressure just before birth and a significant decrease in mean aortic pressure that was evident during the first 9 h after birth. The QT interval was decreased before birth and increased immediately after birth in the newborns of cortisol-treated ewes compared with control lambs. These findings suggest that excess in utero corticosteroid exposure adversely affects fetal cardiac adaptation to extrauterine life and that chronic maternal stress or hypersecretion of corticosteroids may contribute to adverse obstetric outcomes.

Initial Acute Animal Experiment Using a New Miniature Axial Flow Pump in Series With the Natural Heart.

We have advocated an axial flow blood pump called "valvo pump" that is implanted at the aortic valve position, and we have developed axial flow blood pumps to realize the concept of the valvo pump. The latest model of the axial flow blood pump mainly consists of a stator, a directly driven impeller, and a hydrodynamic bearing. The axial flow blood pump has a diameter of 33 mm and length of 74 mm, and the length of anatomical occupation is 33 mm. The axial flow blood pump is anastomosed to the aorta with polytetrafluoroethylene (PTFE) cuffs worn on the inflow and outflow ports. Dp-Q curves of the axial flow blood pump are flatter than those of ordinary axial flow pumps, and pump outflow of 5 L/min was obtained against a pressure difference of 50 mm Hg at a rotational speed of 9000 rpm in vitro. The axial flow blood pump was installed in a goat by anastomosing with the thoracic descending aorta using PTFE cuffs, and it was rotated at a rotational speed of 8000 rpm. Unlike in case of the ventricular assistance in parallel with the natural heart, pulsatilities of aortic pressure and aortic flow were preserved even when the pump was on, and mean aortic flow was increased by 1.5 L/min with increase in mean aortic pressure of 30 mm Hg. In conclusion, circulatory assistance in series with the natural heart using the axial flow blood pump was able to improve hemodynamic pulsatility, and it would contribute to improvement of end-organ circulation. .

Study of the development of the mouse thoracic aorta three-dimensional macromolecular structure using two-photon microscopy.

Using the intrinsic optical properties of collagen and elastin, two-photon microscopy was applied to evaluate the three-dimensional (3D) macromolecular structural development of the mouse thoracic aorta from birth to 60 days old. Baseline development was established in the Scavenger Receptor Class B Type I-Deficient, Hypomorphic Apolipoprotein ER61 (SR-BI KO/ApoeR61(h/h)) mouse in preparation for modeling atherosclerosis. Precise dissection enabled direct observation of the artery wall in situ. En-face, optical sectioning of the aorta provided a novel assessment of the macromolecular structural development. During aortic development, the undulating lamellar elastin layers compressed consistent with the increases in mean aortic pressure with age. In parallel, a net increase in overall wall thickness (p<0.05, in day 60 compared with day 1 mice) occurred with age whereas the ratio of the tunicas adventitia and media to full aortic thickness remained nearly constant across age groups (~1:2.6, respectively). Histochemical analyses by brightfield microscopy and ultrastructure validated structural proteins and lipid deposition findings derived from two-photon microscopy. Development was associated with decreased decorin but not biglycan proteoglycan expression. This non-destructive 3D in situ approach revealed the aortic wall microstructure development. Coupling this approach with the intrinsic optical properties of the macromolecules may provide unique vascular wall 3D structure in many pathological conditions, including aortic atherosclerosis, dissections and aneurysms.

Abstract 18543: Impaired Coronary Metabolic Dilation Leads to Heart Failure During Pressure Overload

The coupling of myocardial blood flow to cardiac work (metabolic dilation) is critical for proper cardiac function. If this coupling is altered, the imbalance could lead micro-areas of hypoxia, ischemia, and fibrosis culminating in heart failure. Accordingly we hypothesized, that when subjected to an extreme metabolic challenge (pressure overload), insufficient dilation of the coronary circulation leads to micro-areas of ischemia and infarction (diffuse fibrosis) and compromised cardiac function. To test this, we studied cardiac function and pathology in Wild Type (WT) and Kv1.5 -/- mice, which have impaired metabolic dilation. To impose a metabolic challenge, transaortic constriction (TAC) was done in Kv1.5 -/- male (n=12), female (n=12) and WT (n=12) mice. TAC increased mean aortic pressure from 98±5 to 142±8 mmHg. Transthoracic echocardiography was performed for evaluation of cardiac function at 7, 28 days after TAC. Masson’s Trichrome and Hypoxyprobe (HP) staining was done at day 28 for evaluation myocardial fibrosis and areas of hypoxia, respectively. After TAC survival rate of Kv 1.5 -/- females was lower (P&lt;0.05) than in males and WT (Panel A). Ejection fraction (EF) was lower (P&lt;0.05) in Kv1.5 -/- (male and female) than WT at all times after TAC (Panel B). In WT, EF was decreased 7 days after TAC, but the reduction was moderate compared to Kv 1.5 -/- . After 28 days of TAC, myocardial fibrosis was markedly higher in Kv1.5 -/- compared to WT (Panel C). In Kv1.5 -/- , fibrosis was in endocardial and perivascular regions, but in WT it was transmural and less developed. HP and DAPI (to locate nuclei) revealed that the number of cells positive for hypoxyprobe was 222% greater in Kv1.5 -/- than in WT, suggesting impaired oxygen delivery. Taken together, we conclude that the absence of Kv1.5 channels, which uncouples myocardial blood flow from cardiac work, compromises coronary and cardiac adaptations to TAC leading to diffuse ischemia, micro-areas of infarction and heart failure. .

Potential negative effects of epinephrine on carotid blood flow and ETCO2 during active compression–decompression CPR utilizing an impedance threshold device

ObjectivesThis study examines the effects of IV epinephrine administration on carotid blood flow (CBF) and end tidal CO2 (ETCO2) production in a swine model of active compression–decompression CPR with an impedance threshold device (ACD-CPR+ITD). MethodsSix female swine (32±1kg) were anesthetized, intubated and ventilated. Intracranial, thoracic aorta and right atrial pressures were measured via indwelling catheters. CBF was recorded. ETCO2, SpO2 and EKG were monitored. V-fib was induced and went untreated for 6min. Three minutes each of standard CPR (STD), STD-CPR+impedance threshold device (ITD) and active compression–decompression (ACD)-CPR+ITD were performed. At minute 9 of the resuscitation, 40μg/kg of IV Epinephrine was administered and ACD-CPR+ITD was continued for 1min. Statistical analysis was performed with a paired t-test. p values of <0.05 were considered statistically significant and all values are reported in mmHg unless otherwise noted. ResultsAortic pressure, cerebral and coronary perfusion pressures increased from STD<STD+ITD<ACD-CPR+ITD (p<0.001). Epinepherine administered during ACD-CPR+ITD signficantly increased mean aortic pressure (29±5 vs 42±12, p=0.01), cerebral perfusion pressure (12±5 vs 22±10, p=0.01), and coronary perfusion pressure (8±7 vs 17±4, p=0.02); however, mean CBF and ETCO2 decreased (respectively 29±15 vs 14±7.0ml/min, p=0.03; 20±7 vs 18±6, p=0.04). ConclusionsIn this model, administration of epinepherine during ACD-CPR+ITD signficantly increased markers of macrocirculation, while significantly decreasing carotid blood flow and ETCO2. This calls into question the ability of calculated perfusion pressures to accurately reflect oxygen delivery to end organs. The administration of epinepherine during ACD-CPR+ITD does not improve cerebral tissue perfusion.

Work-related sickness absence negotiations: GPs' qualitative perspectives

GPs can find their role as issuers of sickness certification problematic, particularly in trying to maintain a balance between certifying absence and preserving the doctor-patient relationship. Little research has been published on consultations in which sickness absence has been certified. To explore negotiations between GPs and patients in sickness absence certification, including how occupational health training may affect this process. A qualitative study was undertaken with GPs trained in occupational health who also participate in a UK wide surveillance scheme studying work-related ill-health. Telephone interviews were conducted with 31 GPs who had reported cases with associated sickness absence. Work-related sickness absence and patients' requests for a 'sick note' vary by diagnosis. Some GPs felt their role as patient advocate was of utmost importance, and issue certificates on a patient's request, whereas others offer more resistance through a greater understanding of issues surrounding work and health acquired through occupational health training. GPs felt that their training helped them to challenge beliefs about absence from work being beneficial to patients experiencing ill-health; they felt better equipped to consider patients' fitness for work, and issued fewer certificates as a result of this. Complex issues surround GPs' role in the sickness-certification process, particularly when determining the patient's ability to work while maintaining a healthy doctor-patient relationship. This study demonstrates the potential impact of occupational health training for GPs, particularly in light of changes to the medical statement introduced in 2010.

Temporary Pulmonary Stent Placement as Emergency Treatment of Pulmonary Embolism: First Experimental Evaluation

We aimed to evaluate the performance of a newly designed temporary stent device as a percutaneous emergency treatment of pulmonary embolism. If thrombolysis is contraindicated or recanalization by thrombolysis delayed in patients with severe pulmonary embolism who are threatened by acute circulatory failure, percutaneous temporary pulmonary stent placement may represent an additional option before surgical embolectomy is considered. The newly designed temporary pulmonary stent is made from woven Nitinol and has a distal blunt end and a proximal crimped end, which is firmly fixed to a 0.035-inch guidewire. It is delivered through a 9.5-F polytetrafluoroethylene sheath using a pusher tube. Stent placement and removal were examined in 9 anesthetized sheep with experimentally induced pulmonary embolism. Hemodynamic parameters were recorded in 7 animals. Delivery and removal of the stent was uneventful and rapidly accomplished. Stent placement was associated with a significant decrease in Miller angiographic index (from 11.2 +/- 3.1 to 3.8 +/- 1.9; p = 0.0001), heart rate (from 139 +/- 35 beats/min to 92 +/- 11 beats/min; p = 0.0129), and mean pulmonary artery pressure (from 32 +/- 14 mm Hg to 21 +/- 14 mm Hg; p = 0.0029) and a significant increase in mean aortic pressure (from 48 +/- 14 mm Hg to 61 +/- 8 mm Hg; p = 0.0080). Autopsy revealed neither wall damage nor parenchymal hemorrhage. Our preliminary study proves the technical feasibility of temporary placement and removal of a newly designed dedicated pulmonary stent to recanalize centrally located embolic occlusions in severe pulmonary embolism. Animal experimental evaluation revealed rapid and significant circulatory improvement after stent placement.

THE HEMODYNAMIC PERFORMANCE OF THE BCM LVAD: AN IN VITRO INVESTIGATION

Purpose: The BCM is a LVAD that is not yet in clinical use and can be operated by counter-pulsation pumps. We aimed to investigate the effect of changing the assistance frequency, heart rate and aortic pressure on the hemodynamic parameters; pressure, flow rate and intensity of waves, generated by BCM. Methods: BCM LVAD has been attached to a true size latex aorta, using water to mimic blood and operated by a counter-pulsation pump. We examined the hemodynamic parameters when changing the assistance frequency of 1:1, 1:2, 1:3, when changing heart rates of 60, 80, 100 using a simulator, and when changing aortic pressure of 6.5 kPa and 8 kPa by increasing the water head. We measured pressure and flow at the ascending aorta and used wave intensity analysis to calculate the energy carried by waves generated by the BCM LVAD. Results: Increasing the assistance frequency increased mean aortic pressure, mean flow rate and the expansion energy, but decreased the compression energy. Increasing heart rate increased mean pressure, mean flow rate and the compression energy but decreased the expansion energy. Increasing aortic pressure increased mean pressure and mean flow rate, although the relative pressure generated by the LVAD decreased. It also increased the compression energy but decreased the expansion energy. Conclusions: The BCM LVAD generates waveforms and hemodynamic parameters similar to those generated by native LVs observed in man and animal of comparable heart rates.

Comparison of Pulsatile With Nonpulsatile Mechanical Support in a Porcine Model of Profound Cardiogenic Shock

The aim of this study was to examine whether pulsatility by intraaortic balloon counterpulsation (IABP) is an important adjunct to the treatment of profound cardiogenic shock (CS) with a widely used, nonpulsatile centrifugal pump (CP). In each of 18 anesthetized, open chest pigs, the outflow cannula of the CP was inserted in the aortic arch through the right external carotid artery, and the inflow cannula of the CP was placed in the left atrium. A 40 cc IABP was subsequently placed in the descending aorta through the left external carotid artery. CS was induced by occlusion of coronary arteries and the infusion of propranolol and crystalloid fluid. Mean aortic pressure, pulse pressure, aortic end diastolic pressure, left ventricular end diastolic pressure, right atrial pressure, and heart rate were monitored. Cardiac output and left anterior descending artery flow were measured with a transit time ultrasound flowmeter. During profound CS, life sustaining hemodynamics were maintained only with the support of the assist devices. Hemodynamic support with the CP was associated with a nearly nonpulsatile flow and a pulse pressure of 7 +/- 4 mm Hg, which increased to 33 +/- 10 mm Hg (p = 0.000) after combining the CP with the IABP. Compared with the hemodynamic support offered by the CP alone, addition of the IABP increased mean aortic pressure from 40 +/- 15 to 50 +/- 16 mm Hg (p = 0.000), cardiac output from 810 +/- 194 to 1,200 +/- 234 ml/min (p = 0.003), and left anterior descending artery flow from 26 +/- 10 to 39 +/- 14 ml/min (p = 0.001). In profound CS, mechanical support provided by a continuous flow CP is enhanced by the added pulsatility of the IABP.

Wave intensity in the ascending aorta: effects of arterial occlusion

We examine the effects of arterial occlusion on the pressure, velocity and the reflected waves in the ascending aorta using wave intensity analysis. In 11 anaesthetised, open-chested dogs, snares were used to produce total arterial occlusion at 4 sites: the upper descending aorta at the level of the aortic valve (thoracic); the lower thoracic aorta at the level of the diaphragm (diaphragm); the abdominal aorta between the renal arteries (abdominal) and the left iliac artery, 2 cm downstream from the aorta iliac bifurcation (iliac). Pressure and flow in the ascending aorta were measured, and data were collected before and during the occlusion. During thoracic and diaphragm occlusions a significant increase in mean aortic pressure (46% and 23%) and in wave speed (25% and 10%) was observed, while mean flow rate decreased significantly (23% and 17%). Also, the reflected compression wave arrived significantly earlier (45% and 15%) and its peak intensity was significantly greater (257% and 125%), all compared with control. Aortic occlusion distal to the renal arteries, however, caused an indiscernible change in the pressure and velocity waveforms, and in the intensities and timing of the waves in the forward and backward directions. The measured pressure and velocity waveforms are the result of the interaction between the heart and the arterial system. The separated pressure, velocity and wave intensity are required to provide information about arterial hemodynamic such as the timing and magnitude of the forward and backward waves. The net wave intensity is simpler to calculate but provides information only about the predominant direction of the waves and can be misleading when forward and backward waves of comparable magnitudes are present simultaneously.

Biventricular support with the Jarvik 2000 axial flow pump: a feasibility study.

Patients with congestive heart failure who are supported with a left ventricular assist device (LVAD) may experience right ventricular dysfunction or failure that requires support with a right ventricular assist device (RVAD). To determine the feasibility of using a clinically available axial flow ventricular assist device as an RVAD, we implanted Jarvik 2000 pumps in the left ventricle and right atrium of two Corriente crossbred calves (approximately 100 kg each) by way of a left thoracotomy and then analyzed the hemodynamic effects in the mechanically fibrillated heart at various LVAD and RVAD speeds. Right atrial implantation of the device required no modification of either the device or the surgical technique used for left ventricular implantation. Satisfactory biventricular support was achieved during fibrillation as evidenced by an increase in mean aortic pressure from 34 mm Hg with the pumps off to 78 mm Hg with the pumps generating a flow rate of 4.8 L/min. These results indicate that the Jarvik 2000 pump, which can provide chronic circulatory support and can be powered by external batteries, is a feasible option for right ventricular support after LVAD implantation and is capable of completely supporting the circulation in patients with global heart failure.

Cardiac contractility modulation by electric currents applied during the refractory period

Inotropic effects of electric currents applied during the refractory period have been reported in cardiac muscle in vitro using voltage-clamp techniques. We investigated how electric currents modulate cardiac contractility in normal canine hearts in vivo. Six dogs were instrumented to measure regional segment length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac contractility modulating (CCM) electric currents (biphasic square pulses, amplitude +/-20 mA, total duration 30 ms) were delivered during the refractory period between pairs of electrodes placed on anterior and posterior walls. CCM significantly increased index of global contractility (E(es)) from 5.9 +/- 2.9 to 8.3 +/- 4.6 mmHg/ml with anterior CCM, from 5.3 +/- 1.8 to 8.9 +/- 4.0 mmHg/ml with posterior CCM, and from 6.1 +/- 2.6 to 11.0 +/- 7.0 mmHg/ml with combined CCM (P < 0.01, no significant change in volume axis intercept). End-systolic pressure-segment length relations showed contractility enhancement near CCM delivery sites, but not remotely. Relaxation was not influenced. CCM increased mean aortic pressure, but did not change peripheral resistance. Locally applied electrical currents enhanced global cardiac contractility via regional changes in myocardial contractility without impairing relaxation in situ.

Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy.

Because nitric oxide (NO) regulates cardiac and vessel contraction, we compared the expression and activity of the endothelial NO synthase (eNOS) and caveolin, which tonically inhibits eNOS in normal and hypertrophic cardiomyopathic hearts. NOS activity (L-[(3)H]citrulline formation), eNOS immunostaining, and caveolin abundance were measured in heart tissue of 23 mongrel dogs before and at 3 and 7 wk of perinephritic hypertension (PHT). Hemodynamic parameters in vivo and endothelial NO-dependent relaxation of macro- and coronary microvessels in vitro were assessed in the same animals. eNOS immunostaining and total calcium-dependent NOS activity decreased at 7 wk in all four heart cavities (in left ventricle, from 17.0 +/- 1.3 to 0.2 +/- 0.2 fmol. min(-1). mg protein(-1), P < 0.001). Caveolin-1 and -3 also decreased in PHT dog hearts. Accordingly, basal vascular tone was preserved, but maximal endothelial NO-dependent relaxation was impaired in all vessels from 7-wk PHT dogs. The latter had preserved systolic function but impaired diastolic relaxation [relaxation time constant (T(1)), 25.1 +/- 0.9 vs. 22.0 +/- 1 ms in controls; P < 0.05]. Peripheral infusion of the NOS inhibitor N(G)-nitro-L-arginine methyl ester increased mean aortic pressure in both groups and reduced diastolic (T(1), 31.9 +/- 1.4 ms) and systolic function in PHT dogs (DP40, 47.5 +/- 2.5 vs. 59.4 +/- 3.8 s(-1) in control animals). In conclusion, both eNOS and caveolin proteins are decreased in the hypertrophic hearts of PHT dogs. This is associated with altered maximal (but not basal) vascular relaxation and impaired diastolic function. Further degradation of cardiac function after NOS inhibition suggests a critical role of residual NOS activity, probably supported by the concurrent downregulation of caveolin.

Role of lipid-derived mediators in tumor necrosis factor-induced endothelin-1 release in vivo.

We hypothesized that endothelin (ET) may be released in response to tumor necrosis factor-alpha (TNF) and that platelet-activating factor (PAF) and cyclooxygenase products modulate TNF-induced ET-1 release in vivo. Anesthetized and instrumented pigs were randomly assigned to receive: 1) saline + TNF (n = 8); 2) saline + heat-inactivated TNF (control group, n = 5); 3) WEB 2086 (PAF receptor antagonist) + TNF (n = 7); or 4) indomethacin + TNF (n = 6). Infusion of TNF was associated with increases in mean aortic, mean pulmonary artery, and intratracheal pressures, increases in systemic and pulmonary vascular resistances, and elevated plasma thromboxane B2 concentration. Plasma ET-1 concentrations were unchanged in controls and significantly increased in TNF-treated pigs at 2 to 4 h. WEB 2086 did not modify plasma levels of ET-1 during exogenous infusion of TNF. In contrast, the cyclooxygenase inhibitor, indomethacin, mildly, but not significantly, reduced plasma ET-1 levels. In addition, indomethacin (but not WEB 2086) blocked or attenuated the TNF-induced increases in mean aortic pressure, systemic vascular resistance, mean pulmonary artery pressure, pulmonary vascular resistance, and intratracheal pressure. We conclude that in the pig, cyclooxygenase products modulate some of the cardiovascular responses to TNF and may mildly affect ET-1 biosynthesis. On the other hand, PAF neither significantly influences TNF-induced biosynthesis of ET-1 nor its associated cardiovascular responses.

Role of inducible nitric oxide synthase in regulation of pulmonary vascular tone in the late gestation ovine fetus.

Nitric oxide (NO) produced by NO synthase (NOS) modulates fetal pulmonary vascular tone and contributes to the fall in pulmonary vascular resistance (PVR) at birth. Although the inducible (type II) NOS isoform is present in human and rat fetal lungs, it is uncertain whether type II NOS activity contributes to vascular NO production in the fetal lung. To determine whether type II NOS is present in the ovine fetal lung and to study the potential contribution of type II NOS on the regulation of basal PVR in the fetus, we measured the hemodynamic effects of three selective type II NOS antagonists: aminoguanidine (AG), 2-amino-5,6-dihydro-6-methyl-4H-1,3 thiazine (AMT), and S-ethylisothiourea (EIT). Studies were performed after at least 72 h of recovery from surgery in 19 chronically prepared fetal lambs (133+/-3 d; 147 d, term). Brief intrapulmonary infusions of AG (140 mg), AMT (0.12 mg), and EIT (0.12 mg) increased basal PVR by 82, 69, and 77%, respectively (P < 0.05). The maximum increase in PVR occurred within 20 min, but often persisted up to 80 min. These agents also increased mean aortic pressure but did not alter the pressure gradient between the pulmonary artery and aorta, suggesting little effect on tone of the ductus arteriosus. Acetylcholine-induced pulmonary vasodilation remained intact after treatment with selective type II NOS antagonists, but not after treatment with the nonselective NOS blocker, nitro-L-arginine. Using Northern blot analysis with poly(A)+ RNA, we demonstrated the presence of two mRNA transcripts for type II NOS (4.1 and 2.6 kb) in the fetal lung. We conclude that the type II NOS isoform is present in the ovine fetal lung, and that selective type II NOS antagonists increase PVR and systemic arterial pressure in the late-gestation fetus. We speculate that type II NOS may play a physiological role in the modulation of vascular tone in the developing fetal lung.

Limitation of cardiac output by a coronary alpha 1-constrictor tone during exercise in dogs.

This study was performed to examine whether an alpha 1-constrictor tone, which limits coronary functional hyperemia during exercise, imposes a significant limitation on global cardiac performance as determined by cardiac output (CO). Seven dogs were chronically instrumented to measure left ventricular pressure (LVP), maximum rate of rise of LVP (dP/dtmax), heart rate (HR), mean aortic pressure (AoP), circumflex blood flow velocity (CFV), and CO at rest and during submaximal exercise. Either the selective alpha 1-adrenergic antagonist prazo (0.5 mg) or the vasodilator adenosine was administered into the circumflex artery during exercise at 6.4 kilometers per hour (kph)/16% treadmill incline. Exercise caused significant increase in mean AoP, HR, LVP, dP/dtmax, CFV, stroke volume (SV), and CO, whereas systemic vascular resistance (SVR) was significantly reduced. After intracoronary alpha 1-blockade with prazosin, CFV, dP/dtmax, SV, and CO increased further (17 +/- 2, 19 +/- 3, 16 +/- 2, and 17 +/- 2%, respectively) without changing mean AoP, HR, or SVR. Comparable increases were observed when CFV was increased by a similar degree using the direct vasodilator adenosine. These results indicate that increasing coronary flow by removing a coronary alpha 1-constrictor tone with prazosin or by direct vasodilation with adenosine during submaximal exercise leads to an increase in myocardial oxygen supply and, as a result, cardiac pump performance (SV and CO).

Endothelium-derived relaxing factor (nitric oxide) has a tonic vasodilating action on coronary collateral vessels

Objectives. We sought to determine whether endothelium-derived relaxing factor (nitrix oxide) exerts a tonic vasodilating effect on coronary collateral channels developed in response to myocardial ischemia.Background. Although the coronary collateral circulation is known to react to several vasoactive agents, the role of endogenously produced nitric oxide is unclear.Methods. Coronary collateral channels were induced in the left circumflex artery bed of 12 chronically instrumented dogs by either ameroid implantation or repeated occlusion of the left circumflex coronary artery. With the native circumflex artery occluded, aortic and circumflex pressures and microsphere flows were measured before and after systemic administration of NG-nitro-l-arginine methyl ester, an arginine analogue known to block the synthesis of nitric oxide.Results. NG-nitro-l-arginine methyl ester increased mean aortic pressure from a mean ± SEM of 92 ± 4 to 114 ± 4 mm Hg, whereas pressure in the occluded circumflex artery decreased from 61 ± 4 to 55 ± 4 mm Hg. The increase in aortic-circumflex pressure gradient (from 31 ± 4 to 59 ± 5 mm Hg) was accompanied by a decrease in flow in the circumflex bed (from 1.31 ± 0.14 to 1.09 ± 0.15 ml/min per g), resulting in an increase in coronary collateral resistance averaging 173 ± 37% (from 26 ± 4 to 64 ± 9 mm Hg/ml per min per g, p < 0.01). The increase in collateral resistance could be partially reversed by administration of l-arginine.Conclusions. We conclude that nitric oxide normally exerts a substantial tonic dilating effect in coronary collateral vessels. Disease-induced alterations in endothelial function may limit collateral perfusion importantly.

Basal Release of Endothelium-Derived Nitric Oxide Plays an Important Role in the Prevention of Afterload Mismatch in Acute Left Ventricular Dysfunction

The basal release of endothelium-derived nitric oxide (EDNO) is considered to play an important role in regulating the vascular tone in normal subjects; however, its role in the presence of acute heart failure is unknown. This study was designed to clarify the role of a basal release of EDNO in the presence of acute heart failure. Acute ischemic left ventricular (LV) dysfunction was produced in 22 dogs by coronary microembolization. After the embolization, only saline solution was intravenously infused for sixty minutes in 10 dogs. In another 12 dogs, NG-monomethyl-L-arginine (L-NMMA), which is known to inhibit the formation of EDNO in the vascular endothelium, was intravenously infused at a rate of 20 micrograms/kg/minute for sixty minutes. Infusion of saline solution did not produce any changes in hemodynamic variables. Infusion of L-NMMA caused increases in mean aortic pressure, systemic vascular resistance, and LV end-diastolic pressure without changes in the LV peak + and - dP/dt (time constant) of LV pressure fall, and these changes were associated with a giant "v" wave in the tracing of left atrial pressure and a decrease in cardiac output. The basal release of EDNO may play an important role in the prevention of afterload elevation, subsequent cardiac output reduction, and afterload mismatch in the presence of acute heart failure.

Benefits of aortic and pulmonary counterpulsation using dynamic latissimus dorsi myoplasty

Intraaortic and pulmonary artery counterpulsation are useful techniques to support circulation during either left or right ventricular dysfunction. Electrically stimulated skeletal muscles wrapped around the aorta, used as means of cardiac failure treatment, have proved to be an effective method of handling experimental left ventricular failure. In this article we report an induced cardiac failure model in acute open chest dogs and describe the hemodynamic improvement of simultaneous aortic and pulmonary artery counterpulsation. This was achieved with a bilateral latissimus dorsi muscle flap, stimulated with a software written in C++ for Windows. Dynamic aortomyoplasty was performed using the left latissimus dorsi muscle flap around the descending aorta, and dynamic pulmonaromyoplasty was achieved wrapping the pulmonary trunk with the right latissimus dorsi muscle flap. In all animals blood pressures and cardiac output were measured after cardiac failure induced by a high-dose of propranolol hydrochloride (3 mg/kg intravenously) before and after latissimus dorsi muscle flap stimulation. Aortopulmonary counterpulsation resulted in a significant increase in mean aortic pressure, mean pulmonary pressure, and cardiac output. In addition, a significant decrease was observed in end-diastolic left ventricular pressure, systemic vascular resistance, and pulmonary vascular resistance. Subendocardial viability index (diastolic pressure-time index/systolic tension-time index) in aortomyoplasty and tension time index in pulmonaromyoplasty showed significant improvement when cardiac assistance was performed by electrical stimulation of both muscles (p = 0.037 and p = 0.001, respectively). Treatment of experimentally induced cardiac failure using aortopulmonary counterpulsation allows effective hemodynamic improvement in open-chest dogs.

Acute phase responses of vasoactive hormones to non pulsatile systemic circulation.

Acute phase responses of vasoactive hormones to the rapid conversion of a systemic flow pattern from pulsatile or non pulsatile mode to the reverse were assessed in 20 goats weighing 45-69 kg. A total left heart bypass was instituted under general anesthesia, with pulsatile and non pulsatile pumps interposed in the circuit in parallel, and the systemic flow mode was rapidly and bidirectionally converted from the pulsatile mode or non pulsatile mode to the reverse. Vasoactive hormone levels and hemodynamics were evaluated before and after 5 min of conversion. No significant difference was observed between the modes either in blood flow or systemic vascular resistance, while the mean aortic pressure was significantly higher in the non pulsatile mode than the pulsatile mode (106.7 +/- 2.4 versus 99.9 +/- 3.5 mmHg). Among various vasoactive hormone levels evaluated, only norepinephrine showed a significant difference between the modes, where concentration in the non pulsatile mode was significantly higher than the pulsatile mode (391.0 +/- 60.7 versus 309.4 +/- 42.5 pg/ml). No correlation was found between the absolute values of mean aortic pressure and norepinephrine level, whereas a significant reciprocal correlation was detected between the magnitude of inter-mode differences in these two parameters. In conclusion, a non pulsatile systemic circulation does not exert significant influence on vasoactive hormone levels, except for slight increase in norepinephrine with a reciprocally correlated increase in mean aortic pressure. It is deduced that activity of the sympathetic nervous system represented by norepinephrine level is higher in the non pulsatile mode than the pulsatile mode, and the baroreceptor reflex functions in an acute phase after flow mode conversion.