Decrease In Total Pulmonary Resistance Research Articles

Pulmonary hemodynamics responses to hypoxia and/or CO2 inhalation during moderate exercise in humans.

In this study, we hypothesized that adding CO2 to an inhaled hypoxic gas mixture will limit the rise of pulmonary artery pressure (PAP) induced by a moderate exercise. Eight 20-year-old males performed four constant-load exercise tests on cycle at 40% of maximal oxygen consumption in four conditions: ambient air, normobaric hypoxia (12.5% O2), inhaled CO2 (4.5% CO2), and combination of hypoxia and inhaled CO2. Doppler echocardiography was used to measure systolic (s)PAP, cardiac output (CO). Total pulmonary resistance (TPR) was calculated. Arterialized blood pH was 7.40 at exercise in ambient and hypoxia conditions, whereas CO2 inhalation and combined conditions showed acidosis. sPAP increases from rest in ambient air to exercise ranged as follows: ambient + 110%, CO2 inhalation + 135%, combined + 184%, hypoxia + 217% (p < 0.001). CO was higher when inhaling O2-poor gas mixtures with or without CO2 (~ 17Lmin-1) than in the other conditions (~ 14Lmin-1, p < 0.001). Exercise induced a significant decrease in TPR in the four conditions (p < 0.05) but less marked in hypoxia (- 19% of the resting value in ambient air) than in ambient (- 33%) and in both CO2 inhalation and combined condition (- 29%). We conclude that (1) acute CO2 inhalation did not significantly modify pulmonary hemodynamics during moderate exercise. (2) CO2 adjunction to hypoxic gas mixture did not modify CO, despite a higher CaO2 in combined condition than in hypoxia. (3) TPR was lower in combined than in hypoxia condition, limiting sPAP increase in combined condition.

(300) - Exercise Hemodynamics in PAH: Lessons Utilizing an Indwelling Hemodynamic Monitor

Pulmonary arterial hypertension (PAH) remains a morbid disease requiring better markers for outcome prediction. Although invasive hemodynamics (Hemos) provides valuable prognostic information, their routine use is impractical. The CardioMEMS™ HF System (CMHFS) is indicated for wireless monitoring of PA pressure in heart failure patients (pts). It allows daily Hemo measurements reflecting the total Hemo burden of disease over time. Importantly, assessment of exercise Hemos may allow a novel modality for assessment of therapeutic interventions in PAH. We tested the feasibility of assessing exercise Hemos in PAH pts implanted with the CMHFS during the 6-minute walk distance (6MWD). 11 PAH pts had the CMHFs implanted. Device mPAP, sPAP, dPAP, HR, and CO (sensor pressure based algorithm) and CMHFS derived total pulmonary resistance (TPR), right ventricular (RV) stroke volume and index (SV, SVI), RV work (W), RV power (P) and compliance (SV/PP) were collected pre and post 6MWD and compared using paired-t tests at 1 & 4 mos. Changes in values b/t 1 and 4 mos were also analyzed. Pts consisted of newly (45%) and previously (55%) diagnosed pts with NYHA Class III or IV sxs. All Implanted pts were female, aged 57 ± 9 with IPAH (45%), scleroderma-related (45%) and anorexigen-related (5%) PAH with a mPAP 45 ± 14 mmHg and pulmonary vascular resistance of 600 ± 384 dyn.s.cm-5. There were no peri-procedural complications and no device related SAE’s within the first month post implant. PAH meds were optimized per the treating MD over time. As compared to pre 6MWD Hemos, there was a significant increase (p <0.05) in post 6MWD HR, TPR, sPAP, dPAP, mPAP, RVW and RVP and a significant decrease (p<0.05) in SV, SVI and C. These changes persisted at 4 mos. When comparing changes in isolated pre and post 6MWD values between 1 and 4 mos, there were no differences in pre 6MWD values. However, significant positive changes (p<0.05) in post 6MWD SV, SVI, RVW occurred with a consequent significant decrease in TPR. Use of the CMHFS in a select group of PAH pts with advanced symptoms appears safe and demonstrated with exercise a significant increase in pulmonary pressure and resistance with a coincident decline in RV performance, coupling and efficiency that persisted over time and only marginally improved with optimization of therapy. The clinical impact on these changes will need to be further explored.

A new era of therapeutic strategies for chronic thromboembolic pulmonary hypertension by two different interventional therapies; pulmonary endarterectomy and percutaneous transluminal pulmonary angioplasty.

BackgroundPulmonary endarterectomy (PEA) is established for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Recently, percutaneous transluminal pulmonary angioplasty (PTPA) has been added for peripheral-type CTEPH, whose lesions exist in segmental, subsegmental, and more distal pulmonary arteries. A shift in clinical practice of interventional therapies occurred in 2009 (first mainly PEA, later PTPA). We examined the latest clinical outcomes of patients with CTEPH.Methods and ResultsThis study retrospectively included 136 patients with CTEPH. Twenty-nine were treated only with drug (Drug-group), and the other 107 underwent interventional therapies (Interventions-group) (39 underwent PEA [PEA-group] and 68 underwent PTPA [PTPA-group]). Total 213 PTPA sessions (failures, 0%; mortality rate, 1.47%) was performed in the PTPA-group (complications: reperfusion pulmonary edema, 7.0%; hemosputum or hemoptysis, 5.6%; vessel dissection, 2.3%; wiring perforation, 0.9%). Although baseline hemodynamic parameters were significantly more severe in the Interventions-group, the outcome after the diagnosis was much better in the Interventions-group than in the Drug-group (98% vs. 64% 5-year survival, p<0.0001). Hemodynamic improvement in the PEA-group was a 46% decrease in mean pulmonary arterial pressure (PAP) and a 49% decrease in total pulmonary resistance (TPR) (follow-up period; 74.7±32.3 months), while those in the PTPA-group were a 40% decrease in mean PAP and a 49% decrease in TPR (follow-up period; 17.4±9.3 months). The 2-year survival rate in the Drug-group was 82.0%, and the 2-year survival rate, occurrence of right heart failure, and re-vascularization rate in the PEA-group were 97.4%, 2.6%, and 2.8%, and those in the PTPA-group were 98.5%, 2.9%, and 2.9%, respectively.ConclusionThe patients who underwent interventional therapies had better results than those treated only with drugs. The availability of both of these operative and catheter-based interventional therapies leads us to expect the dawn of a new era of therapeutic strategies for CTEPH.

Pulmonary vascular resistances during exercise in normal subjects: a systematic review

The physiological range of pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR), and the impact of exercise, age and posture have been a matter of debate for many years. We performed a systematic literature review including all right heart catheterisation data where individual PVR and TPR of healthy subjects both at rest and exercise were available. Data were stratified according to age, exercise level and posture. Supine resting PVR in subjects aged <24 yrs, 24-50 yrs, 51-69 yrs and ≥70 yrs was 61±23, 69±28, 86±15 and 90±39 dyn·s·cm(-5), respectively. Corresponding TPR was 165±50, 164±46, 226±64 and 223±45 dyn·s·cm(-5), respectively. During moderate exercise in subjects aged ≤50 yrs, an 85% increase in cardiac output was associated with a 25% decrease in TPR (p<0.0001) and a 12% decrease in PVR (p<0.01). At 51-69 yrs of age there was no significant decrease in TPR and PVR. In individuals aged ≥70 yrs TPR even increased by 17% (p=0.01), while PVR did not change significantly. At higher exercise levels, TPR decreased in all age groups. In the upright position, based on a limited number of data, resting TPR and PVR were higher than in the supine position and decreased more prominently during exercise, suggesting the release of resting pulmonary vasoconstriction. These data may form a basis to define normal PVR at rest and exercise.

‘Raising the bar’ for the treatment of pulmonary arterial hypertensionThe opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

Historically, idiopathic pulmonary arterial hypertension (IPAH, formerly referred to as primary pulmonary hypertension) has been considered a fatal disease. The natural history of IPAH was well described by the American National Institutes of Health (NIH) Registry of the 1980s. A median survival of 2.8 years with estimated single-year survival rates at 1, 3, and 5 years of 68, 48, and 35%, respectively were documented. Predictors of a poor prognosis included advanced functional class and haemodynamics (right atrial pressure, cardiac index, and pulmonary artery pressure). Fortunately, much has changed since the 1980s. We now several novel therapeutic options including prostacyclins, endothelin receptor antagonists, and phosphodiesterase type-5 inhibitors, all of which have improved exercise endurance in clinical trials. Surely, we have improved survival in IPAH, haven’t we? Classically, controlled clinical trials in pulmonary arterial hypertension (PAH) have studied the primary endpoint of 6-min walk distance over a short duration (12–16 weeks). Regulatory authorities have accepted the 6-min walk distance as a reliable and reproducible indicator of drug efficacy. Withholding therapy for more than 12–16 weeks was felt to be unethical, particularly early on, when the most ill patients were being entered into clinical trials. The only randomized controlled trial to ever demonstrate a survival benefit in IPAH was the open label trial with intravenous (IV) epoprostenol reported by Barst et al. In that 81-patient trial, 8 patients, all of whom were randomized to conventional therapy alone, died over the 12-week study, resulting in a mortality of 20%. Notably, a quarter of the patients in that trial were functional class IV at baseline. Subsequent open label observational experiences have also demonstrated a survival benefit with IV epoprostenol, either compared with historical controls, or the expected survival based on the NIH equation. Despite this apparent survival benefit, the 3-year survival with IV epoprostenol monotherapy in both these series of functional class III and IV IPAH patients was 63%. In both series, functional class was predictive of survival, both at the initiation of therapy, and when assessed after 3 or more months of therapy. Consequently, and appropriately, the most ill patients are no longer entered into clinical trials, but are treated with active medications. With less ill patients in clinical trials, over short periods of time, other therapies such as bosentan, sildenafil, treprostinil, and iloprost have established improvements in 6-min walk, leading to regulatory approval. The important question of longer term outcomes has not been answered by these brief trials. Provencher et al. describe the long-term outcomes of 103 consecutive functional class III and IV IPAH patients treated with the oral endothelin receptor antagonist, bosentan, as first-line therapy. Using a stringent treatment algorithm, additional therapy with prostanoids (primarily IV epoprostenol) was recommended for patients with functional class IV symptoms on treatment, or persistent functional class III symptoms after at least 4 months of treatment, together with (1) a 6-min walk distance of ,250 m; (2) a .10% decrease in 6-min walk distance from the previous value in two tests performed at least 2 weeks apart; or (3) a cardiac index of ,2.2 L min m. At 4 months, improvements in 6-min walk distance (42 m) and haemodynamics were similar to the findings of the randomized controlled trials. Functional class improved in 48% of patients, remained stable in 42%, and deteriorated in 9%. Overall survival estimates at 1 and 2 years were 90 and 87%, respectively. However, event-free survival estimates were 61 and 44% at 1 and 2 years, respectively. During the mean follow-up period of 24+ 15 months, 13 patients died (8 after the initiation of a prostanoid) and 36 were treated with a prostanoid. Prostanoid therapy was proposed to an additional nine patients who either declined (n 1⁄4 5) or were unable to manipulate the complex delivery system (n 1⁄4 4). Important predictors of outcome included the 6-min walk distance and right atrial pressure at baseline, and the 6-min walk distance, increase in 6-min walk distance, and decrease in total pulmonary resistance at 4 months of therapy. These overall survival data are similar to those previously reported among the 169 IPAH patients who were followed in an open label fashion after

805-2 Faster but not more Complete Thrombolysis with Tissue Plasminogen Activator than with Streptokinase in Massive Pulmonary Embolism

Mean pulmonary artery pressure (MPA), cardiac output (CO), and right ventricular ejection fraction (RVEF) were serially assessed with use of a 5-way, rapid response rate, Swan-Ganz catheter in 45 Pts submitted to thrombolytic therapy (TI) for massive pulmonary embolism (PE) defined as Miller score &lt; 17/34, and mean pulmonary artery pressure &gt;20 mmHg. Total pulmonary resistance (TPR) was determined from MPA and CO and expressed in dynes/sec/cm -5 . Pulmonary angiography was performed before and 24 after TT. Streptokinase (STK) was used in 22 Pts, and tissue plasminogen activator (t-PA) in 23. T 0 T 1 h T2 h T 12 h TPR-STK 701 ± 261 591 ± 203 583 ± 211 380 ± 155 TPR-t-PA 735 ± 390 508 ± 330 405 ± 210 * 338 ± 142 RVEF-STK 0.18 ± 0.02 0.20 ± 0.07 020 ± 0.09 026 ± 0.10 RVEF-t-PA 0.18 ± 0.08 024 ± 0.09 0.27 ± 0.09 * 029 ± 0.09 * p &lt; 0.05 between STK and t-PA A significant decrease in TPR inversely correlated to a significant increase in RVEF occurred in both treatment groups, but significantly more rapidly in the t-PA group than in the STK group. The difference was significant 2 hand 4 h after onset of TT, but had vanished at 12 h. Miller score, similar in both groups before TT, was identical in both groups at 24 h. t-PA induced a significantly faster hemodynamic improvement than STK in massive PE, but with a catch-up phenomenon apparent 12 h after onset of therapy.

Pulmonary mechanics and energetics in preterm infants who had respiratory distress syndrome treated with synthetic surfactant

Pulmonary mechanics and energetics were determined in 32 neonates with respiratory distress syndrome, who were randomly assigned to receive treatment with an exogenous synthetic surfactant, Exosurf Neonatal, or air placebo. Pulmonary mechanics were measured before and 2 hours after surfactant (n = 13) or air placebo (n = 19) treatment, then longitudinally at 24, 48, and 72 hours after treatment, and again at 7, 14, and 28 days of age. There were no significant differences in the values for pulmonary mechanics or energetics 2 hours after the first dose of surfactant. Improvement in pulmonary mechanics was apparent 24 hours after surfactant treatment, when dynamic compliance was 36% greater than in the placebo group (p less than 0.03). Lung compliance values were also higher in surfactant-treated infants 48 and 72 hours after treatment, with a maximal increase of 64% at 7 days of age (p less than 0.03). Surfactant treatment also caused a significant decrease in total pulmonary resistance at 48 and 72 hours after initial treatment and at 14 days of age (p less than 0.04). Similarly, a decrease in flow-resistive work of breathing was demonstrated 24, 48, and 72 hours after surfactant treatment. At 28 days of age, pulmonary mechanics were not different in the two groups. We conclude that beneficial effects of surfactant on pulmonary mechanics were not apparent 2 hours after dosing but were evident 24 hours after dosing and persisted for the first 7 to 14 days of life.

Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: A European multicenter double-blind trial

Twelve centers participated in a double-blind study in which 63 patients with angiographically documented acute massive pulmonary embolism were randomly assigned to treatment with either urokinase (4,400 U/kg as an intravenous bolus infusion, then 4,400 U/kg per h over 12 h; n = 29) or alteplase (10 mg as an intravenous bolus infusion, then 90 mg over 2 h) followed by heparin (n = 34). The primary objective was to compare the resolution of pulmonary embolism as judged by the change in total pulmonary resistance over the initial 2 h. Further objectives were to evaluate the changes in total pulmonary resistance over the next 10 h and the degree of angiographic resolution at 12 to 18 h.At 2 h, total pulmonary resistance decreased by 18 ± 22% in the urokinase group and by 36 ± 17% in the alteplase group (p = 0.0009). Continuous monitoring of pulmonary artery mean pressure, cardiac index and total pulmonary resistance revealed that these variables improved faster in the alteplase group, with consistently significant intergroup differences from 30 min up to 3 to 4 h.After 12 h, the decrease in total pulmonary resistance was 53 ± 19% in the urokinase group compared with 48 ± 17% in the alteplase group and the reduction in the angiographic severity score was 30 ± 25% compared with 24 ± 18%, respectively, with no significant intergroup differences. Bleeding was equally frequent in the two treatment groups, except that more urokinasetreated patients experienced hematomas at puncture sites.

A comparison of the acute hemodynamic effects of prostacyclin and hydralazine in primary pulmonary hypertension

In patients with primary pulmonary hypertension the administration of a vasodilating drug is often used to test pulmonary vasoreactivity. Hydralazine has been employed as a test drug, but because of its long duration of action there is a risk of sustained systemic arterial hypotension in patients with a fixed pulmonary vascular resistance. In this study we compared the acute hemodynamic effects of intravenous prostacyclin, a potent, short-acting vasodilator, with the effects of oral or intravenous hydralazine. Both prostacyclin and hydralazine increased cardiac output and decreased systemic pressure without changing pulmonary arterial pressure in seven patients with primary pulmonary hypertension. The average decrease in total pulmonary resistance with prostacyclin (−46% ± 5%) was more than that with hydralazine (−32% ± 6%). The respective decreases in total systemic resistance were −50% ± 4% vs −43% ± 6%. The percent changes in individual responses to the two agents were correlated (p < 0.05) for pulmonary arterial pressure, systemic arterial pressure, total pulmonary resistance, and total systemic resistance. We concluded that the pulmonary hemodynamic effects of prostacyclin resembled those of hydralazine. Prostacyclin may predict the acute pulmonary hemodynamic effects of hydralazine in primary pulmonary hypertension and because of its prompt, brief action may provide greater patient safety.

Stimulation of group III and IV muscle afferents reflexly decreases total pulmonary resistance in dogs

Although previous investigations have shown that stimulating group III and IV afferents reflexly decreased transverse tension from the trachealis muscle, these measurements provided no functional information about airway caliber. We therefore electrically stimulated gracilis muscle afferents in paralyzed, chloralose anesthetized dogs while recording total pulmonary resistance breath by breath. In addition, we recorded compound action potentials to determine which afferents were stimulated by current intensities of 3, 5, 20, 70 and 200 times motor threshold. We found that stimulating (20 Hz) the nerves at 3 times threshold, a current intensity which activated only group I and II afferents, had no effect on total pulmonary resistance, whereas stimulating teh nerves at 5, 20 and 70 times threshold, current intensities which activated group I, II and III afferents, significantly decreased this variable. Stimulating the nerves at 200 times threshold, a current intensity which activated group IV as well as group I, II and III afferents, decreased total pulmonary resistance significantly more than did stimulating the nerves at 5, 20 or 70 times threshold. In addition stimulating the nerves at 200 times threshold but at frequencies of 2 and 5 Hz significantly decreased total pulmonary resistance. The decrease in total pulmonary resistance evoked by electrically stimulating the nerves at 200 times threshold was unaffected by propranolol but was abolished by atropine methylnitrate. We conclude that stimulating group III and IV gracilis muscle afferents in dogs reflexly decreases total pulmonary resistance, an effect due to the withdrawal of a tonic cholinergic input to the airways.

The acute effects of low flow oxygen and isosorbide dinitrate on left and right ventricular ejection fractions in chronic obstructive pulmonary disease

The objectives of this study were to determine the effects of low flow oxygen and isosorbide dinitrate on rest and exercise biventricular ejection fractions in patients with chronic obstructive pulmonary disease and to relate these ejection fraction responses to changes in pressure and flow. Nine patients with stable, moderate to severe chronic obstructive pulmonary disease who had no prior history of heart failure performed supine exercise with simultaneous hemodynamic and radionuclide ventriculographic monitoring. Eight patients performed a second exercise during low flow oxygen breathing and five performed a third exercise after ingesting 10 mg oral isosorbide. Oxygen led to a decrease in exercise pulmonary artery pressure in all subjects and a decline in total pulmonary resistance in five of the seven in whom it was measured. Right ventricular ejection fraction increased 0.05 or more only in subjects who had a decrease in total pulmonary resistance. Isosorbide fed to an increase in rest and exercise right and left ventricular ejection fractions with simultaneous decreases in pulmonary artery pressure, total pulmonary resistance, blood pressure and arterial oxygen tension. These results suggest that in patients with chronic obstructive pulmonary disease but without a history of right heart failure, the right ventricular systolic functional response to low flow oxygen and isosorbide at rest and exercise is, in part, determined by changes in total pulmonary resistance. The chronic relation between right ventricular ejection fraction and pulmonary hemodynamics in patients with chronic obstructive pulmonary disease remains to be evaluated.

Hemodynamics at rest and during exercise after oral hydralazine in patients with cor pulmonale

Oral hydralazine has been shown to be effective in decreasing pulmonary arteriolar resistance and increasing cardiac output in some patients with primary pulmonary hypertension. To determine whether a similar response could be observed in patients with chronic cor pulmonale, the hemodynamic status before and after the oral administration of hydralazine (25 mg, then 50 mg every 6 hours for 48 hours) were evaluated in 12 patients at rest and in 8 during upright exercise. After hydralazine, there was an increase in cardiac output at rest, from 4.3 to 6.3 liters/min (p <0.001), and reductions in arterlovenous oxygen difference, from 8.1 to 6.1 volume percent (p <0.001), mean pulmonary arterial pressure, from 52 to 44 mm Hg (p <0.01), and pulmonary arteriolar resistance, from 11.2 to 6.2 units (p <0.0005). Similar hemodynamic changes occurred during exercise, including an increase in pulmonary arterial saturation from 27 to 39 percent (p <0.001) and a decrease in total pulmonary resistance from 12.7 to 8.9 units (p <0.01). Results of pulmonary function tests performed before and after hydralazine did not change with drug administration. These findings indicate that the lung vascular bed in some patients with cor pulmonale is capable of responding to hydralazine with a reduction in pulmonary resistance and an increase in cardiac output both at rest and during exercise.