Impact of calcium-channel blockers on right heart function in a controlled model of chronic pulmonary hypertension

Andreas Zierer, Rochus K. Voeller, Spencer J. Melby, Paul Steendijk, Marc R. Moon

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background and objective: Patients with chronic pulmonary hypertension (CPH) who demonstrate pulmonary vasodilation following calcium-channel blocker (CCB) administration are defined as 'responders'. In contrast, 'nonresponders' are patients who do not show such pulmonary vasodilation with CCB therapy. The purpose of this investigation was to study the effects of CCB therapy on right heart mechanics in experimental CCB responders versus CCB nonresponders. Methods: In 12 dogs, right atrial (RA) and ventricular pressure and volume (conductance catheters) were simultaneously recorded after 3 months of progressive pulmonary artery banding. Diltiazem was given at 10mghS1 with the pulmonary artery constricted (simulated CCB nonresponder). Responders were then created by releasing the pulmonary artery band to unload the ventricle. RA and right ventricular contractility and diastolic stiffness (slope of end-systolic and end-diastolic pressure-volume relations) were calculated and RA reservoir and conduit function were quantified as RA inflow with the tricuspid valve closed compared with open, respectively. Results: With CCB, RA contractility (P<0.03) and cardiac output (P<0.004) were compromised in simulated nonresponders whereas RA stroke work was pharmacologically depressed in the setting of an unchanged afterload. After simulating a responder by controlled pulmonary artery band release, the right atrium became less distensible, causing a shift from reservoir to conduit function (P<0.001) towards physiological baseline conditions and a recovery in the hyperdynamic compensatory response in both chambers (P<0.007) as evidenced by declined RA and right ventricular contractility with an improved cardiac output ascompared with CPH and simulated nonresponders. RA and right ventricular diastolic function in both groups was not affected by CCB. Conclusion: CCB did not affect right ventricular function in simulated nonresponders but significantly impaired RA contractility and cardiac output. In simulated responders, afterload fell substantially, thereby allowing the right atrium and right ventricle to recover from their pathological hyperdynamic contractile response to CPH. This effect outweighed the intrinsic negative effects of CCB therapy on systolic RA function. Current data suggest that the right atrium in CPH is much more sensitive to CCB therapy than the right ventricle and show for the first time why CCB therapy in CPH has been empirically restricted to documented responders.

Original languageEnglish (US)
Pages (from-to)253-259
Number of pages7
JournalEuropean Journal of Anaesthesiology
Volume26
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • Calcium-channel blockers
  • Chronic pulmonary hypertension
  • Right heart function

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