Elsevier

Transplantation Proceedings

Volume 39, Issue 10, December 2007, Pages 3142-3149
Transplantation Proceedings

Kidney transplantation
Complication: Nephropathy
Acute Effects of a Single Dose of Phosphodiesterase Type 5 Inhibitor (Sildenafil) on Systemic Arterial Blood Pressure During Exercise and 24-Hour Ambulatory Blood Pressure Monitoring in Heart Transplant Recipients

https://doi.org/10.1016/j.transproceed.2007.04.029Get rights and content

Abstract

Background

Arterial systemic hypertension (SH) can be associated with a decrease in endothelium-dependent nitric oxide (NO). Sildenafil increases cyclic guanosine monophosphate (cGMP), a mediator of NO. However, little is known about the effects of PDE5 inhibition on 24-hour ambulatory pressure (ABP) and exercise blood pressure, noreprinephrine (Nor), and exercise capacity, especially after orthotopic heart transplantation (OHT).

Methods

We studied 22 OHT patients who on the 1st day underwent a cardiopulmonary (CP) self-controlled treadmill 6′ walk test (6′) and, then, an ECG monitored CP treadmill maximal exercise test (Ex) within 60 and 90 minutes after oral Sildenafil (Sil; 50 mg) or placebo (Pl) given at random, and ABP. We determined at basal position (b), in the last minute of the 6′ and at the peak Ex, the HR (bpm), Systolic blood pressure (SBP), and diastolic blood pressure (DBP), (mm Hg), VO2 (mL/kg/min), Slope VE/VCO2, exercise time (ET, min), distance (D; miles), and Nor (pg/mL). Also, after CP tests, 24-h SBP and DBP, the measurements were repeated on the 2nd day when the cross-over was done.

Results

Sil significantly reduced blood pressure in the basal position and during exercise. It also promoted a significant reduction in SBP and DBP during 24 hours, daytime and nighttime. Sil did not change exercise capacity.

Conclusion

The NO-cGMP pathway seems to play a role in blood pressure control in OHT. In addition to antihypertensive therapy, PDE5 inhibition may have potential beneficial effects on hypertensive OHT.

Section snippets

Study Subjects

We analyzed patients who underwent OHT with at least 1 year follow-up. Twenty-four orthotopic heart transplant recipients were consecutively selected for the study (Table 1). Seventeen hypertensive patients, defined as 24-hour blood pressure >140/90 mm Hg, were presented antihypertensive medications. All patients were in stable clinical condition without required changes in treatment within the last 3 months. The protocol was approved by the Ethical Review Committee of the Heart Institute

Results

Twenty-two patients completed the Sil and Pl phases of the protocol. Two men were excluded during the Pl phase, due to an episode of intense fatigue and headache. Seventeen patients who had a diagnosis of systemic hypertension were receiving antihypertensives. Five patients had normal systemic blood pressure. Patients underwent the 6-minute cardiopulmonary treadmill walking test 70 ± 12 minutes after Pl oral ingestion, and 71 ± 11 minutes after Sil (P = not significant [NS]). The maximal

HR, SBP, and DBP

In comparison with Pl, Sil did not change the heart rate at rest, last minute heart rate in the 6-minute cardiopulmonary walking test, or during the peak maximal cardiopulmonary treadmill exercise tests (Table 2).

The 50 mg Sil dose reduced the systemic SBP and DBP at rest and exercise in both tests. In hypertensive subjects, Sil decreased both systemic SBP and DBP at rest, during the 6-minute walking test, and maximal exercise. In normotensive patients, Sil reduced the systemic DBP at the last

Discussion

Our results demonstrated that 50 mg Sil, a selective PDE5 inhibitor, reduced systemic SBP and DBP at rest, during exercise, and during 24-hour monitoring after OHT, mainly among hypertensive OHT patients. Sil did not change the heart rate, the VE/VCO2 slope, the VO2, or the exercise capacity during both exercise tests. Sil was well tolerated and increased resting neurohormonal activation as measured by Nor plasma levels.

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