Abstract
Aims: We aimed at investigating contractile changes after hypoxia- reoxygenation and dobutamine challenge in superfused human atrial pectinate muscle to see whether high versus low stimulation rate during hypoxia might account for outcome differences compatible with the definition of an in vitro model of myocardial stunning and whether pretreatment with the dihydropyridine Ca2+ entry blocker felodipine might afford protection. Methods: Human right atrial trabeculae obtained from adult patients were superfused in an organ bath with oxygenated (O2 content 16 ml/l) and modified (NaHCO3 25.7 mmol/l) Tyrode's solution at 37°(2. Dobutamine (1 nmol/l to 10 μmol/l) was superfused in 10 oxygenated preparations to select the optimal drug concentration to be used in another 22 which were randomized. Group (A) consisted of time-related controls (Tyrodes's solution for 225 min at cycle length (CL) 1600 ms and no dobutamine). There were two test groups, respectively. (B) low (1600 ms CL) and (C) high (400 ms CL) stimulation rate. After 60 min of stabilization, in groups B and C, hypoxic superfusion (O2 content 5 ml/l) lasted 60 min, then reoxygenation (60 min) and dobutamine challenge (1 μmol/l, 15 min) were performed. Analysis of variance for repeated measures with the Greenhouse-Geisser correction, and a repeated measures model with structured covariance (preparation mass, length, width and time-varying time to peak tension) matrices were used whereby grouping (G), time (T) and G T interaction were weighted. Force-frequency relationship and post-pausal potentiation were studied after each phase. Electrophysiology, histomorphometry and electron microscopy were carried out (n = 6). Felodipine (0.1 μmol/l, n = 5) pretreatment (15 min before hypoxia) was given in parallel experiments. Results: Time-related controls showed ≃10% per hour decrease of developed tension and the Paradise test provided ≃80% of control values. In test groups (as compared to baseline values) contractility was decreased ≃65% after hypoxia-reoxygenation and it increased ≃25% after dobutamine (G, 0.00652+-related diastolic processes thus helping index myocardial contractile reserve. Force-frequency relationship was negative at high stimulation rates, concomitant to an abrupt change of shape and duration of action potential with little time for Ca2+- related Ca2+ release and ensuing systolic processes. Felodipine pretreatment enabled an unblunted response to dobutamine. Histomorphometry showed an unexpected 'fibrotic core'. At electron microscopy, subendocardial and deep part of the same pectinate muscles showed identical degrees of degenerative lesions. Superfused samples showed, unexpectedly, less anoxic lesions than preparations fixed within 15 min from surgical explant, although lesions were higher than in samples fixed immediately after explant. Conclusions: This might be a relevant model, whereby pharmacological or physical interventions are tested. Native human atrial trabeculae might be used without dissection and/or preservatives. If high stimulation rate during hypoxia is used the power of hypothesis testing is maximized. Future studies with this material will be easier and comparatively smaller series might be investigated. Felodipine at low concentration was protective in this model.
| Original language | English |
|---|---|
| Pages (from-to) | 107-132 |
| Number of pages | 26 |
| Journal | International Journal of Cardiology |
| Volume | 62 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Nov 20 1997 |
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Keywords
- Analysis of variance
- Calcium-entry blockers
- Developed tension
- Electron microscopy
- Felodipine
- Force-frequency relationship
- Greenhouse-Geisser correction
- Histomorphometry
- Human atrial contractility
- Human atrial electrophysiology
- Human atrial trabeculae
- Hypoxia
- Myocardial protection
- Post-pausal potentiation
- Reoxygenation injury
- Stunning
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Felodipine protects human atrial muscle from hypoxia-reoxygenation dysfunction : A force-frequency relationship study in an in vitro model of stunning. / Iwashiro, Katsunori; Criniti, Anna; Sinatra, Riccardo; Dawodu, Amos Adeyemo; D'Amati, Giulia; Monti, Francesco; Pannarale, Luigi; Bernucci, Paola; Brancaccio, Gian Luca; Vetuschi, Antonella; Gaudio, Eugenio; Gallo, Pietro; Puddu, Paolo Emilio.
In: International Journal of Cardiology, Vol. 62, No. 2, 20.11.1997, p. 107-132.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Felodipine protects human atrial muscle from hypoxia-reoxygenation dysfunction
T2 - A force-frequency relationship study in an in vitro model of stunning
AU - Iwashiro, Katsunori
AU - Criniti, Anna
AU - Sinatra, Riccardo
AU - Dawodu, Amos Adeyemo
AU - D'Amati, Giulia
AU - Monti, Francesco
AU - Pannarale, Luigi
AU - Bernucci, Paola
AU - Brancaccio, Gian Luca
AU - Vetuschi, Antonella
AU - Gaudio, Eugenio
AU - Gallo, Pietro
AU - Puddu, Paolo Emilio
PY - 1997/11/20
Y1 - 1997/11/20
N2 - Aims: We aimed at investigating contractile changes after hypoxia- reoxygenation and dobutamine challenge in superfused human atrial pectinate muscle to see whether high versus low stimulation rate during hypoxia might account for outcome differences compatible with the definition of an in vitro model of myocardial stunning and whether pretreatment with the dihydropyridine Ca2+ entry blocker felodipine might afford protection. Methods: Human right atrial trabeculae obtained from adult patients were superfused in an organ bath with oxygenated (O2 content 16 ml/l) and modified (NaHCO3 25.7 mmol/l) Tyrode's solution at 37°(2. Dobutamine (1 nmol/l to 10 μmol/l) was superfused in 10 oxygenated preparations to select the optimal drug concentration to be used in another 22 which were randomized. Group (A) consisted of time-related controls (Tyrodes's solution for 225 min at cycle length (CL) 1600 ms and no dobutamine). There were two test groups, respectively. (B) low (1600 ms CL) and (C) high (400 ms CL) stimulation rate. After 60 min of stabilization, in groups B and C, hypoxic superfusion (O2 content 5 ml/l) lasted 60 min, then reoxygenation (60 min) and dobutamine challenge (1 μmol/l, 15 min) were performed. Analysis of variance for repeated measures with the Greenhouse-Geisser correction, and a repeated measures model with structured covariance (preparation mass, length, width and time-varying time to peak tension) matrices were used whereby grouping (G), time (T) and G T interaction were weighted. Force-frequency relationship and post-pausal potentiation were studied after each phase. Electrophysiology, histomorphometry and electron microscopy were carried out (n = 6). Felodipine (0.1 μmol/l, n = 5) pretreatment (15 min before hypoxia) was given in parallel experiments. Results: Time-related controls showed ≃10% per hour decrease of developed tension and the Paradise test provided ≃80% of control values. In test groups (as compared to baseline values) contractility was decreased ≃65% after hypoxia-reoxygenation and it increased ≃25% after dobutamine (G, 0.00652+-related diastolic processes thus helping index myocardial contractile reserve. Force-frequency relationship was negative at high stimulation rates, concomitant to an abrupt change of shape and duration of action potential with little time for Ca2+- related Ca2+ release and ensuing systolic processes. Felodipine pretreatment enabled an unblunted response to dobutamine. Histomorphometry showed an unexpected 'fibrotic core'. At electron microscopy, subendocardial and deep part of the same pectinate muscles showed identical degrees of degenerative lesions. Superfused samples showed, unexpectedly, less anoxic lesions than preparations fixed within 15 min from surgical explant, although lesions were higher than in samples fixed immediately after explant. Conclusions: This might be a relevant model, whereby pharmacological or physical interventions are tested. Native human atrial trabeculae might be used without dissection and/or preservatives. If high stimulation rate during hypoxia is used the power of hypothesis testing is maximized. Future studies with this material will be easier and comparatively smaller series might be investigated. Felodipine at low concentration was protective in this model.
AB - Aims: We aimed at investigating contractile changes after hypoxia- reoxygenation and dobutamine challenge in superfused human atrial pectinate muscle to see whether high versus low stimulation rate during hypoxia might account for outcome differences compatible with the definition of an in vitro model of myocardial stunning and whether pretreatment with the dihydropyridine Ca2+ entry blocker felodipine might afford protection. Methods: Human right atrial trabeculae obtained from adult patients were superfused in an organ bath with oxygenated (O2 content 16 ml/l) and modified (NaHCO3 25.7 mmol/l) Tyrode's solution at 37°(2. Dobutamine (1 nmol/l to 10 μmol/l) was superfused in 10 oxygenated preparations to select the optimal drug concentration to be used in another 22 which were randomized. Group (A) consisted of time-related controls (Tyrodes's solution for 225 min at cycle length (CL) 1600 ms and no dobutamine). There were two test groups, respectively. (B) low (1600 ms CL) and (C) high (400 ms CL) stimulation rate. After 60 min of stabilization, in groups B and C, hypoxic superfusion (O2 content 5 ml/l) lasted 60 min, then reoxygenation (60 min) and dobutamine challenge (1 μmol/l, 15 min) were performed. Analysis of variance for repeated measures with the Greenhouse-Geisser correction, and a repeated measures model with structured covariance (preparation mass, length, width and time-varying time to peak tension) matrices were used whereby grouping (G), time (T) and G T interaction were weighted. Force-frequency relationship and post-pausal potentiation were studied after each phase. Electrophysiology, histomorphometry and electron microscopy were carried out (n = 6). Felodipine (0.1 μmol/l, n = 5) pretreatment (15 min before hypoxia) was given in parallel experiments. Results: Time-related controls showed ≃10% per hour decrease of developed tension and the Paradise test provided ≃80% of control values. In test groups (as compared to baseline values) contractility was decreased ≃65% after hypoxia-reoxygenation and it increased ≃25% after dobutamine (G, 0.00652+-related diastolic processes thus helping index myocardial contractile reserve. Force-frequency relationship was negative at high stimulation rates, concomitant to an abrupt change of shape and duration of action potential with little time for Ca2+- related Ca2+ release and ensuing systolic processes. Felodipine pretreatment enabled an unblunted response to dobutamine. Histomorphometry showed an unexpected 'fibrotic core'. At electron microscopy, subendocardial and deep part of the same pectinate muscles showed identical degrees of degenerative lesions. Superfused samples showed, unexpectedly, less anoxic lesions than preparations fixed within 15 min from surgical explant, although lesions were higher than in samples fixed immediately after explant. Conclusions: This might be a relevant model, whereby pharmacological or physical interventions are tested. Native human atrial trabeculae might be used without dissection and/or preservatives. If high stimulation rate during hypoxia is used the power of hypothesis testing is maximized. Future studies with this material will be easier and comparatively smaller series might be investigated. Felodipine at low concentration was protective in this model.
KW - Analysis of variance
KW - Calcium-entry blockers
KW - Developed tension
KW - Electron microscopy
KW - Felodipine
KW - Force-frequency relationship
KW - Greenhouse-Geisser correction
KW - Histomorphometry
KW - Human atrial contractility
KW - Human atrial electrophysiology
KW - Human atrial trabeculae
KW - Hypoxia
KW - Myocardial protection
KW - Post-pausal potentiation
KW - Reoxygenation injury
KW - Stunning
UR - http://www.scopus.com/inward/record.url?scp=0031442059&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031442059&partnerID=8YFLogxK
U2 - 10.1016/S0167-5273(97)00189-7
DO - 10.1016/S0167-5273(97)00189-7
M3 - Article
C2 - 9431863
AN - SCOPUS:0031442059
VL - 62
SP - 107
EP - 132
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
IS - 2
ER -