Decrease In Right Ventricular Pressure Research Articles

CAR Selectively Enhances the Pulmonary Vasodilatory Effect of Fasudil in a Microsphere Model of Pulmonary Hypertension.

Despite the approval of several medications for pulmonary hypertension, morbidity and mortality are unacceptably high. Systemic hypotension may limit the use of pulmonary hypertension medications. This study aimed to assess whether the homing peptide CAR (CARSKNKDC) improves the vasodilatory selectivity of fasudil in the pulmonary circulation or systemic circulation in a porcine pulmonary hypertension model. Pulmonary hypertension (to approximately 2/3-3/4 systemic pressure levels) was induced by chronic and acute administration of microspheres in 3 micro Yucatan pigs (mean weight 19.9 kg, mean age 4.3 months). Fasudil (0.3 mg/kg) was administered without and with CAR (1.5 mg/kg), and the effect on aortic (Ao) and right ventricular (RV) pressure was recorded with indwelling catheters. Immediately after fasudil administration, there was a decrease in Ao pressure followed by prompt recovery to baseline. The RV pressure decrease was progressive and sustained. Fasudil alone resulted in a 12% decrease in RV pressure, whereas co-administration of CAR with fasudil resulted in a 22% decrease in RV pressure (p < 0.0001). Fasudil alone caused an average decrease of 34% in the RV/Ao pressure ratio, and fasudil + CAR caused an average decrease of 40% in the RV/Ao pressure ratio (p < 0.0001). The homing peptide CAR selectively enhanced the acute vasodilatory effects of fasudil on the pulmonary vascular bed in a porcine experimental model of pulmonary hypertension.

A closer look at physiological indicators of cardiovascular function post‐transplantation

A closer look at physiological indicators of cardiovascular function post‐transplantation

Trimedazidine alleviates pulmonary artery banding-induced acute right heart dysfunction and activates PRAS40 in rats.

The molecular mechanism underlying acute right heart failure (RHF) is poorly understood. We used pulmonary artery banding (PAB) to induce acute RHF characterized by a rapid rise of right ventricular pressure, and then a decrease in right ventricular pressure along with a decrease in blood pressure right after banding. We found higher brain natriuretic peptide (BNP) and beta-myosin heavy chain (βMHC) levels and lower alpha-myosin heavy chain (αMHC) levels in RHF rats than sham-operated rats. Hemodynamic indexes in rats with acute RHF were slightly improved by trimedazidine TMZ, a key inhibitor of fatty acid (FA) oxidation. TMZ also reversed downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC-1β) and peroxisome proliferator-activated receptor alpha (PPARα) by PAB and up-regulates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor delta (PPARδ) and pyruvate dehydrogenase kinase isoform 4 (PDK4). In addition, TMZ reversed upregulation of phosphorylated Akt by PAB and increased phosphorylated proline-rich Akt-substrate 40 (PRAS40). Autophagy and apoptosis were not modified by PAB or TMZ. An acute RHF model was established in rats through 70% constriction of the pulmonary artery. TMZ treatment alleviated PAB-induced acute RHF by activating PRAS40 and upregulatingPGC-1α, PGC-1β, PPARα, PPARδ, and PDK4.

A novel open chest method of right ventricular hemodynamics measurement in pulmonary hypertensive mice

Objective: Right heart catheterization is the gold-standard for measurement of right ventricular hemodynamics. However, it is difficult to perform in mice. We thus aimed to establish a new open chest method to record and analyze the right ventricular hemodynamic parameters in intubated mice connected to a respirator under anesthesia. Methods: Eight-week old male C57BL/6 mice were divided into the control group, and the hypoxia group using completely random method. Mice in the hypoxia group were exposed in low pressure oxygen chamber, which simulated the environment of plateau (5 500 m altitude, 10% oxygen) for 3 weeks. Mice in the control group were exposed in normal pressure and oxygen environment. The mice were intratracheally intubated and connected to a respirator, chest was opened, right ventricular hemodynamics were measured with a needle (0.7 mm×19 mm) punctured into right ventricle (5 mm in death), which was connected to the measuring equipment. Results: The open chest procedure could be finished within 5-10 minutes. The successful rate was 100%. There was no significant difference in heart rate between control group and hypoxia group under anesthetia ((306.4±11.5) bpm vs.(320.4±16.0) bpm, P>0.05). Compared with the control group, both the right ventricular systolic pressure (RVSP) and the mean right ventricular pressure(mRVP)were increased in hypoxia group ((17.1±1.0)mmHg(1 mmHg=0.133 kPa) vs. (22.6±1.0) mmHg, P<0.01; (9.6±0.8) mmHg vs.(12.4±0.3) mmHg, P<0.01). Moreover, the absolute value of the maximal rate of increase in right ventricular pressure (dp/dtmax) and the maximal rate of decrease in right ventricular pressure (dp/dtmin) were higher in the hypoxia group ((421.3±30.6)mmHg/s vs.(639.7±47.7)mmHg/s, P<0.01; (-324.3±24.0)mmHg/s vs. (-496.5±40.6) mmHg/s, P<0.01), indicating the pathological status after hypoxia treatment. Conclusions: Right ventricular hemodynamics measurement with this open chest technique is easy to handle and can accurately reflect the right ventricular pressure in mice under physiological and pathological conditions.

Endovascular Treatment of a Large Iliac Vein Aneurysm and High-Flow Arteriovenous Fistula

Iliac arteriovenous fistulas (AVFs) are rare but can cause significant morbidity. This report illustrates the endovascular management of a patient with an iliac vein aneurysm caused by an AVF. A 35-year-old pregnant woman was found on routine ultrasound examination to have a left 4.5-cm aortoiliac aneurysm. Past medical history included anxiety, obesity, Lyme disease, methadone use, and hypothyroidism. In addition, she had four emergency department visits during a 2.5-year period leading to diagnoses of pulmonary hypertension (right ventricular pressure of 62 mm Hg) and high-output heart failure of unclear etiology requiring chronic diuresis. Her surgical history included lumbar disk surgery and two cesarean sections. She had no history of abdominal trauma. On examination, she had lower extremity swelling and a pulsating abdominal mass. Because of the high-risk nature of the pregnancy, elective termination was recommended and subsequently performed. Computed tomography angiography showed a left common iliac vein aneurysm measuring 5.5 × 4.2 cm (Fig) and a left common iliac artery to common iliac vein AVF with associated mega cava. The AVF was thought to be related to prior spine surgery. The patient underwent percutaneous endovascular repair of the AVF with placement of a bifurcated aortic AFX stent graft (Endologix, Irvine, Calif). As the AVF was close to the left iliac artery bifurcation, the left internal iliac artery was embolized with an Amplatzer plug (St. Jude Medical, St. Paul, Minn) and the stent graft extended to the left external iliac artery. Completion angiography showed resolution of the AVF. Recovery was uneventful, and the patient was discharged on a 3-month course of coumadin to prevent thrombosis. She had complete resolution of cardiopulmonary symptoms with a decrease in right ventricular pressure to 30 mm Hg at 2 months after the procedure. Computed tomography angiography at 6 months showed no evidence of AVF and shrinkage of the left iliac vein aneurysm to 2.5 cm (Fig). AVF can unusually present as a venous aneurysm. Endovascular treatment of the AVF can resolve the aneurysm and reverse systemic hemodynamic changes.

Cardiovascular effects of pimobendan in healthy mature horses.

Pimobendan is an inodilator used in dogs for the management of heart failure due to myxomatous valve disease or dilated cardiomyopathy. The lack of data regarding the effects of pimobendan in horses prevents the rational use of this drug. To determine the cardiovascular effects of pimobendan in healthy mature horses. Randomised experimental study. Five horses were fasted overnight prior to receiving i.v. pimobendan (0.25 mg/kg bwt), intragastric (i.g.) pimobendan (0.25 mg/kg bwt) or i.g. placebo with a washout period of one week between each administration. Horses were instrumented for the measurement of right ventricular (RV) minimum pressure, RV maximum pressure, RV end diastolic pressure, and maximum rate of increase and decrease in RV pressure before and 0.5, 1, 2, 4, and 8 h after drug administration. Arterial blood pressure, central venous pressure, cardiac output and heart rate were measured at the same time points. Data were expressed as a maximum percentage of change over baseline values. There were no adverse effects associated with administration of pimobendan. The percentage increase in heart rate was significantly greater for horses given pimobendan i.g. (33 ± 4%) and i.v. (36 ± 14%) than for those given a placebo (-2 ± 7%). The percentage increase in maximum rate of increase in RV pressure (35 ± 36%) and the percentage decrease in minimum pressure (47 ± 24%) and end diastolic pressure (34 ± 13%) were significantly greater in horses given pimobendan i.v. than in those given placebo. Other variables measured were not significantly different between treatment groups. Pimobendan administered i.v. has positive chronotropic and inotropic effects in healthy mature horses and warrants further investigation for the treatment of heart failure in horses.

The Beneficial Impact of Fasudil and Sildenafil on Monocrotaline-Induced Pulmonary Hypertension in Rats: A Hemodynamic and Biochemical Study

Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT.

Surgical reconstruction of peripheral pulmonary artery stenosis in Williams and Alagille syndromes

Peripheral pulmonary artery stenosis is a rare congenital heart defect frequently found in association with Williams and Alagille syndromes. Controversy exists regarding the optimal treatment of peripheral pulmonary artery stenosis, with most centers favoring catheter-based interventions. In contrast, we have preferentially used surgical reconstruction of peripheral pulmonary artery stenosis. The purpose of the present study was to review our experience with surgical reconstruction of peripheral pulmonary artery stenosis. We performed a retrospective review of patients who underwent surgical reconstruction of peripheral pulmonary artery stenosis. A total of 16 patients were identified: 7 had Williams syndrome, 6 had Alagille syndrome, and 3 had no identifiable syndrome. Detailed pulmonary angiography was performed in all patients to define stenoses at the main, branch, lobar, and segmental arterial levels. The mean preoperative right ventricular/left ventricular pressure ratio was 0.88 ± 0.07. The surgical approach was a median sternotomy with cardiopulmonary bypass. All peripheral stenoses were augmented with pulmonary artery homograft tissue. The median age at surgery was 14 months, and concomitant procedures were performed in 9 of the 16 patients. There was 1 operative mortality (6%). The mean right ventricular/left ventricular pressure ratio decreased to 0.40 ± 0.04 postoperatively (P < .005), representing a 55% reduction compared with the preoperative values. The patients were followed up for a median of 5 years. No late mortality occurred and reoperation was not required. The data have demonstrate that this comprehensive surgical approach to the treatment of peripheral pulmonary artery stenosis was associated with low early and no late mortality. Surgical reconstruction of the peripheral pulmonary artery stenosis resulted in a significant decrease in right ventricular pressure. We hypothesize that this reduction in right ventricular pressures will confer a long-term survival advantage for this cohort of patients.

Prospective Evaluation of the Balloon‐to‐Annulus Ratio for Valvuloplasty in the Treatment of Pulmonic Stenosis in the Dog

Background: In dogs, treatment of pulmonic valve stenosis (PS) with pulmonary balloon valvuloplasty (PBV) is a viable method to decrease the pressure gradient across the valve. However, to the authors' knowledge, the variables that influence the selection of the correct balloon size for the procedure have not been explored. Moreover, the lesions caused by the procedure have not been detailed. Hypothesis: Variables that influence the measurement of the annulus could affect selection of the balloon size. We sought to determine the effects of treatment when the balloon‐to‐annulus ratio (BAR) was or &gt; 1.3, but within the recommended range of 1.2–1.5, regardless of whether dilation was performed with single or double balloon technique. Animals: Twenty‐five Beagles with PS were studied. Methods: Inter‐and intra‐observer variability, echocardiography versus angiocardiography, and systolic versus diastolic timing were evaluated for the BAR. Assessment of right ventricular (RV) pressure, Doppler gradient, stenotic valve area, and RV wall thickness were compared before and 1, 90, and 180 days after treatment. Postmortem examination of the heart was done. Results: Significant correlations existed in measurement of the annulus; however, variation existed that would change balloon size. Improvement in the degree of PS was significant regardless of the BAR or single or double ballooning. In the most severely affected dogs, continued improvement was noted on day 90. Postmortem examination revealed tears in the commissures and the valve leaflets. Conclusions: Multiple factors influenced determination of the BAR and a range of 1.2–1.5 was effective without detrimental consequences. Dogs with severe PS had continued decrease in RV pressure 3 months after treatment.

Prospective Evaluation of the Balloon-to-Annulus Ratio for Valvuloplasty in the Treatment of Pulmonic Stenosis in the Dog

In dogs, treatment of pulmonic valve stenosis (PS) with pulmonary balloon valvuloplasty (PBV) is a viable method to decrease the pressure gradient across the valve. However, to the authors' knowledge, the variables that influence the selection of the correct balloon size for the procedure have not been explored. Moreover, the lesions caused by the procedure have not been detailed. Variables that influence the measurement of the annulus could affect selection of the balloon size. We sought to determine the effects of treatment when the balloon-to-annulus ratio (BAR) was or > 1.3, but within the recommended range of 1.2-1.5, regardless of whether dilation was performed with single or double balloon technique. Twenty-five Beagles with PS were studied. Inter- and intra-observer variability, echocardiography versus angiocardiography, and systolic versus diastolic timing were evaluated for the BAR. Assessment of right ventricular (RV) pressure, Doppler gradient, stenotic valve area, and RV wall thickness were compared before and 1, 90, and 180 days after treatment. Postmortem examination of the heart was done. Significant correlations existed in measurement of the annulus; however, variation existed that would change balloon size. Improvement in the degree of PS was significant regardless of the BAR or single or double ballooning. In the most severely affected dogs, continued improvement was noted on day 90. Postmortem examination revealed tears in the commissures and the valve leaflets. Multiple factors influenced determination of the BAR and a range of 1.2-1.5 was effective without detrimental consequences. Dogs with severe PS had continued decrease in RV pressure 3 months after treatment.

Natural history of supravalvular aortic stenosis and pulmonary artery stenosis

Data from 35 patients with supravalvular aortic stenosis or pulmonary artery stenosis, or both, undergoing cardiac catheterization between 1973 and 1989 were analyzed retrospectively. Twenty-seven patients had supravalvular aortic stenosis:11 required surgery after the first investigation and 8 (80%) of 10 others undergoing serial investigation showed an increase in the left ventricle to aorta pressure gradient. Angiographic measurements showed that the increase in the aortic pressure gradient was related to failure of normal growth of the ascending aorta lumen.Nineteen patients had pulmonary artery stenosis, with a right ventricular pressure greater than 33 on Hg. At restudy, right ventricular pressure had decreased in 9 (82%) of 11 patients. This decrease in right ventricular pressure was associated with an increase in the systolic distensibility of the proximal pulmonary arteries, although there was no increase in the idiastolic diameters. One patient had a rapid early increase in right ventricular pressure and no pulmonary artery growth. In two patients, multiple peripheral pulmonary artery stenoses became evident with time and produced persistent right ventricular hypertension.Supravalvular aortic stenosis is usually a progressive lesion,, with an increase in left ventricular outflow tract pressure gradient related to poor growth of the ascending aorta. Pulmonary artery stenosis usually improves and only rarely limits prognosis.

Changes in myocardial repolarization in patients undergoing balloon valvuloplasty for congenital pulmonary stenosis: evidence for contraction-excitation feedback in humans.

Alterations in ventricular loading conditions lead to changes in action potential duration and arrhythmias via contraction-excitation feedback; a decrease in load leads to prolongation of repolarization. To determine whether changes in right ventricular load alter ventricular repolarization in man, the corrected QT interval, a measure of overall ventricular repolarization, was measured in 32 patients before and after valvuloplasty for pulmonary stenosis. Right ventricular systolic pressure decreased (82.5 +/- 30.7 to 40.5 +/- 9.5 mm Hg, p less than .001) and the QTc increased concurrently (409.1 +/- 24.3 to 440.7 +/- 28.0 msec, p less than .001) after successful valvuloplasty. The increase in QTc was most marked for those patients with a greater than 30 mm Hg decrease in right ventricular pressure (40.0 +/- 23.3 vs 16.3 +/- 21.3 msec, p = .006). In a subset of seven patients in whom monophasic action potentials were recorded, monophasic action potential duration, a measure of local repolarization, was prolonged (230.0 +/- 24.3 vs 216.9 +/- 21.9, p less than .001) after successful valvuloplasty, confirming that the QTc prolongation reflected changes in local ventricular repolarization. In addition, during nine acute right ventricular outflow tract occlusions in a subset of six patients, monophasic action potential duration shortened (206.6 +/- 17.6 vs 221.7 +/- 20.9 msec, p less than .01) and early afterdepolarizations developed consistent with contraction-excitation feedback. These data suggest that, in humans, changes in mechanical load are associated with changes in ventricular repolarization consistent with contraction-excitation feedback.

Postoperative long-term results in total correction of tetralogy of Fallot: with special reference to method and degree of relief of right ventricular outflow tract obstruction.

Late results were studied in 63 patients who underwent complete repair of tetralogy of Fallot. Mild pulmonary stenosis (PS) was present in 73%, moderate PS in 17% and severe PS in 10% of the patients. When a transannular patch was used, wider enlargement of the pulmonary annulus did not always relate to a decrease in right ventricular pressure and right ventricular to pulmonary artery pressure gradient in the late postoperative period. Pulmonary regurgitation (PR) of grade 2 or less did not relate to the late postoperative hemodynamics and cardiac function. PR of grade 3 or over led to right ventricular and pulmonary artery hypertension, and to increases in right ventricular end-diastolic volume and CTR. PR of grade 4 impaired left ventricular function. PR of grade 3 or over with moderate PS led to elevation in right ventricular end-diastolic pressure. In patients with mild PS and PR of grade 2 or less, late postoperative hemodynamics and cardiac function were excellent. To maintain excellent postoperative hemodynamics and cardiac function, it is imperative to obtain PR of grade 2 or less and to use a procedure which will lead to excellent development of the pulmonary annulus. In conventional procedures using a transannular patch, a CSAI of less than 2.5 cm2/m2 and precise coaptation between the original pulmonary cusp and the cusp mounted on the patch will aid in avoiding significant PR.

Partial extracorporeal circulation in closed-chest dogs.

In anesthetized dogs a fraction of the venous blood flow was diverted into a heart-lung machine (gas exchange bag) and from there infused by gravity into the arterial circulation. During such a partial heart-lung bypass an increase in extracorporeal perfusion rate resulted in a long lasting bradycardia and a decrease of right ventricular pressure and pulmonary blood flow. The decline of the aortic pressure caused by this maneuver could be compensated by adjustment of the infusion pressure into the arterial system. The external work of the heart was reduced thereby without compromising tissue perfusion. The procedure was compatible with survival of the animals. Submitted on February 24, 1959